Graft-vs-host Disease and Toxic Epidermal Necrolysis Following Hematopoietic Stem Cell Transplantation

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Graft-vs-host Disease and Toxic Epidermal Necrolysis Following Hematopoietic Stem Cell Transplantation

To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.1 Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.2 However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

Desquamation and erosions involving the face as well as the oral and nasal mucosae
FIGURE 1. Desquamation and erosions involving the face as well as the oral and nasal mucosae (patient 1).

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.5 In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease
FIGURE 2. Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease (patient 1)(H&E, original magnification ×200).

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis
FIGURE 3. Four weeks after treatment, histopathology revealed a vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis (patient 1)(H&E, original magnification ×200).

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.2 Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.6-8

Morbilliform exanthem without desquamation
FIGURE 4. Morbilliform exanthem without desquamation (patient 2).

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.9 Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.10

The rash evolved to full-thickness epidermal detachment within 48 hours
FIGURE 5. The rash evolved to full-thickness epidermal detachment within 48 hours (patient 2).

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.11 Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.12

 

 

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.13 Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.14 Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.1 These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

References
  1. Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15:1555-1562.
  2. Jeanmonod P, Hubbuch M, Grünhage F, et al. Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation. Transpl Infect Dis. 2012;14:422-426.
  3. Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278-283.
  4. Scott-Lang V, Tidman M, McKay D. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31:532-534.
  5. Kingpin T, Mahasirimongkol S, Konyoung P, et al. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics. 2015;25:402-411.
  6. Correia O, Delgado L, Barbosa IL, et al. Increased interleukin 10, tumor necrosis factor alpha, and interleukin 6 levels in blister fluid of toxic epidermal necrolysis. J Am Acad Dermatol. 2002;47:58-62.
  7. French LE, Tschopp J. Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition. Schweiz Med Wochenschr. 2000;130:1656-1661.
  8. Downey A, Jackson C, Harun N, et al. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol. 2012;66:995-1003.
  9. de Araujo E, Dessirier V, Laprée G, et al. Death ligand TRAIL, secreted by CD1a+ and CD14+ cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis. Exp Dermatol. 2011;20:107-112.
  10. Viard-Leveugle I, Gaide O, Jankovic D, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133:489-498.
  11. Choi SW, Levine JE, Ferrara JL. Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am. 2010;30:75-101.
  12. Markey KA, Burman AC, Banovic T, et al. Soluble lymphotoxin is an important effector molecule in GVHD and GVL. Blood. 2010;115:122-132.
  13. Dodiuk-Gad RP, Olteanu C, Jeschke MG, et al. Treatment of toxic epidermal necrolysis in North America. J Am Acad Dermatol. 2015;73:876-877.
  14. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
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From the Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine, Tampa.

The authors report no conflict of interest.

Correspondence: Lucia Seminario-Vidal, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 79, Tampa, FL 33612 (luciasem@usf.health.edu).

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From the Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine, Tampa.

The authors report no conflict of interest.

Correspondence: Lucia Seminario-Vidal, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 79, Tampa, FL 33612 (luciasem@usf.health.edu).

Author and Disclosure Information

From the Department of Dermatology and Cutaneous Surgery, University of South Florida College of Medicine, Tampa.

The authors report no conflict of interest.

Correspondence: Lucia Seminario-Vidal, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of South Florida, 12901 Bruce B. Downs Blvd, MDC 79, Tampa, FL 33612 (luciasem@usf.health.edu).

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To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.1 Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.2 However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

Desquamation and erosions involving the face as well as the oral and nasal mucosae
FIGURE 1. Desquamation and erosions involving the face as well as the oral and nasal mucosae (patient 1).

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.5 In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease
FIGURE 2. Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease (patient 1)(H&E, original magnification ×200).

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis
FIGURE 3. Four weeks after treatment, histopathology revealed a vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis (patient 1)(H&E, original magnification ×200).

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.2 Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.6-8

Morbilliform exanthem without desquamation
FIGURE 4. Morbilliform exanthem without desquamation (patient 2).

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.9 Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.10

The rash evolved to full-thickness epidermal detachment within 48 hours
FIGURE 5. The rash evolved to full-thickness epidermal detachment within 48 hours (patient 2).

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.11 Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.12

 

 

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.13 Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.14 Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.1 These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

To the Editor:

Acute graft-vs-host disease (GVHD) remains a limitation to hematopoietic stem cell transplantation (HSCT) in 20% to 50% of patients after transplant. Furthermore, failed treatment with corticosteroids is frequent and portends a poor prognosis.1 Toxic epidermal necrolysis (TEN) is an epidermolytic skin disorder thought to represent an adverse drug reaction, though its pathogenesis remains unclear. Severe forms of acute GVHD can mimic TEN clinically and histologically. Both can present with widespread cutaneous and mucosal bullae, erosions, and desquamation. Toxic epidermal necrolysis in the context of allogeneic hematopoietic stem cell transplantation is extremely rare, with almost 100% mortality in adult patients. Features that favor acute GVHD over TEN include diarrhea, elevation in bilirubin level, and chimerism.2 However, these features might be absent, posing a therapeutic dilemma, as current treatment preferences for each of these entities differ.

Growing evidence supports the use of anti–tumor necrosis factor (TNF) α drugs for the treatment of TEN. Success has been reported with both anti–TNF-α monoclonal antibodies as well as the soluble fusion protein etanercept.3,4 The use of TNF-α inhibitors in acute GVHD remains anecdotal.

Desquamation and erosions involving the face as well as the oral and nasal mucosae
FIGURE 1. Desquamation and erosions involving the face as well as the oral and nasal mucosae (patient 1).

A 58-year-old man (patient 1) with a history of acute myelogenous leukemia presented with a pruritic morbilliform eruption 28 days after HSCT. There was no desquamation or mucosal involvement and the biopsy obtained was histologically suggestive of grade 2 acute GVHD. His immunosuppressive regimen included sirolimus and cyclophosphamide. He was receiving trimethoprim-sulfamethoxazole (TMP-SMX), voriconazole, and acyclovir for infectious prophylaxis. At the time of presentation, he was treated with high-dose systemic steroids (prednisone 2 mg/kg/d) for acute GVHD with partial improvement. Upon tapering of the steroids 3 weeks after initiating TMP-SMX and 1 week after initiating voriconazole, he developed painful desquamation and erosions involving 95% of the body surface area (BSA), necessitating admission to the local burn unit (Figure 1). Biopsies demonstrated full-thickness epidermal necrosis with subepidermal blistering and interface dermatitis (Figure 2). No gastrointestinal tract involvement of acute GVHD was noted. The patient was a 100% donor chimera, supporting the diagnosis of acute GVHD; however, the patient and donor carried the HLA-C*06:02 allele, which previously has been described in association with TMP-SMX–related Stevens-Johnson syndrome/TEN.5 In addition, causality assessment using the algorithm of drug causality for epidermal necrolysis indicated TMP-SMX as a probable cause and voriconazole as a possible cause. The diagnosis of TEN with a SCORe of Toxic Epidermal Necrosis (SCORTEN) of 4 in the setting of acute GVHD was favored, though grade 4 acute GVHD could not be excluded. Trimethoprim-sulfamethoxazole was discontinued, and voriconazole was changed to posaconazole. He received supportive care along with 1 dose of 25-mg subcutaneous etanercept and 3 days of intravenous immunoglobulin (IVIG). Skin re-epithelialization was complete by 3 weeks. At 4 weeks, the patient developed a new asymptomatic erythematous eruption. Biopsies demonstrated changes of acute and chronic GVHD (Figure 3) that resolved with up-titration of sirolimus. The patient remained hospitalized for 96 days and continued to follow up with his transplant team as well as ophthalmology and dermatology. He died 2 years after HSCT.

Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease
FIGURE 2. Histopathology revealed full-thickness epidermal necrosis suggesting toxic epidermal necrolysis or grade 4 acute graft-vs-host disease (patient 1)(H&E, original magnification ×200).

A 67-year-old woman (patient 2) with high-grade myelodysplastic syndrome presented with an erythematous morbilliform eruption on the torso on day 20 after a matched unrelated HSCT that histologically was consistent with grade 2 GVHD (Figure 4). She had been receiving sirolimus and tacrolimus for GVHD prophylaxis. Infectious prophylaxis included acyclovir, pentamidine, micafungin, and TMP-SMX. Despite high-dose systemic steroids, the rash progressed and ultimately involved 80% BSA. A positive Nikolsky sign was noted involving 21% BSA (Figure 5), in addition to oral and genital mucosal ulcers. She denied nausea, vomiting, fever, or diarrhea. Chimerism studies were negative. Trimethoprim-sulfamethoxazole was discontinued, and she was transferred to a burn unit. Biopsies showed full-thickness epidermal necrosis. A diagnosis of TEN with a SCORTEN of 4 in the setting of acute GVHD was favored; grade 4 acute GVHD could not be excluded. Steroids were discontinued. Because laboratory studies indicated IgA deficiency, IVIG was not considered as a systemic option for therapy. The patient received 1 dose of infliximab (5 mg/kg). Cyclophosphamide 1600 mg weekly was added for GVHD therapy. The wounds progressively healed, and 2 weeks into her admission she was noted to have only 3% BSA with denuded skin. The patient was transferred to the cancer treatment center for further management of the malignancy. Unfortunately, after 2 months she died due to ischemic colitis that was confirmed on autopsy.

Vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis
FIGURE 3. Four weeks after treatment, histopathology revealed a vacuolar interface with scattered necrotic keratinocytes within an acanthotic epidermis with hyperkeratosis and wedge-shaped hypergranulosis (patient 1)(H&E, original magnification ×200).

Graft-vs-host disease and TEN are rare, life-threatening complications seen in patients with allogeneic HSCT.2 Graft-vs-host disease and TEN share clinicopathologic characteristics and effector immune mechanisms, largely the substantial role of T-cell activation and tissue destruction, which occur through mediators such as TNF-α.6-8

Morbilliform exanthem without desquamation
FIGURE 4. Morbilliform exanthem without desquamation (patient 2).

Given the sparse lymphocytic infiltrate, keratinocyte death in TEN is thought to result from soluble molecules, including TNF-α and TNF-related apoptosis-inducing ligand.9 Tumor necrosis factor α has been identified in blister fluid, biopsy specimens, and serum of patients with TEN. Tumor necrosis factor α increases the expression of keratinocyte-inducible nitric oxide synthase, which upregulates keratinocyte Fas ligand expression and subsequent Fas- and caspase-8–mediated keratinocyte cell death.10

The rash evolved to full-thickness epidermal detachment within 48 hours
FIGURE 5. The rash evolved to full-thickness epidermal detachment within 48 hours (patient 2).

Acute GVHD results from donor lymphocyte activation after infusion into damaged recipient tissues that previously have been radiated or chemoablated. Mismatches in histocompatibility complexes between donor cells and recipient tissue antigens serve as the initial trigger for immune activation. Activation of antigen-presenting cells followed by activation, proliferation, differentiation, and migration of donor T cells ultimately results in destruction of the target tissue.11 Immune mediators, such as TNF-α and lymphotoxin α (another member of the TNF superfamily), play a nonredundant role in the pathogenesis of GVHD.12

 

 

Current treatment strategies for severe acute GVHD and TEN differ. In North America, high-dose IVIG frequently is used as first-line systemic therapy, while high-dose systemic corticosteroids rarely are used.13 Studies have demonstrated successful use of anti–TNF-α drugs for the treatment of TEN.3,4 Moreover, etanercept has shown to effectively inhibit lymphotoxin α.14 Similarly, TNF inhibition in the management of steroid-refractory acute GVHD has been successful.1 These studies coupled with the underlying immune mechanisms that both diseases share encouraged initiating a trial of anti–TNF-α therapy in our patients.

Patient 1 merits further discussion because he was both a 100% donor chimera as well as a carrier of an human leukocyte antigen susceptibility candidate allele to TMP-SMX. Historical features of his presentation are consistent with either steroid-refractory GVHD or TEN superimposed on acute GVHD. His initial presentation of the more typical macular exanthem of cutaneous acute GVHD was both biopsy proven and supported by clinical improvement with steroid therapy, which was later followed by a robust blistering mucocutaneous presentation approximately 3 weeks after the administration of TMP-SMX and 1 week after initiating voriconazole that improved with IVIG and etanercept.

It is difficult to determine if TEN represents a continuum or result of the underlying drivers of acute GVHD vs a drug reaction. Although there is insufficient evidence to establish a clear-cut diagnosis of TEN, these cases illustrate the need for better diagnostic techniques to allow differentiation between TEN and grade 4 acute GVHD, and in the context of uncertainty, TNF-α inhibition poses a viable therapeutic strategy for these 2 often lethal conditions. Our cases do unequivocally indicate the benefit of this therapeutic modality, add to the current body of literature supporting the use of TNF-α inhibitors in patients such as ours without an official TEN diagnosis, and may guide future investigative efforts.

References
  1. Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15:1555-1562.
  2. Jeanmonod P, Hubbuch M, Grünhage F, et al. Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation. Transpl Infect Dis. 2012;14:422-426.
  3. Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278-283.
  4. Scott-Lang V, Tidman M, McKay D. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31:532-534.
  5. Kingpin T, Mahasirimongkol S, Konyoung P, et al. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics. 2015;25:402-411.
  6. Correia O, Delgado L, Barbosa IL, et al. Increased interleukin 10, tumor necrosis factor alpha, and interleukin 6 levels in blister fluid of toxic epidermal necrolysis. J Am Acad Dermatol. 2002;47:58-62.
  7. French LE, Tschopp J. Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition. Schweiz Med Wochenschr. 2000;130:1656-1661.
  8. Downey A, Jackson C, Harun N, et al. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol. 2012;66:995-1003.
  9. de Araujo E, Dessirier V, Laprée G, et al. Death ligand TRAIL, secreted by CD1a+ and CD14+ cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis. Exp Dermatol. 2011;20:107-112.
  10. Viard-Leveugle I, Gaide O, Jankovic D, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133:489-498.
  11. Choi SW, Levine JE, Ferrara JL. Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am. 2010;30:75-101.
  12. Markey KA, Burman AC, Banovic T, et al. Soluble lymphotoxin is an important effector molecule in GVHD and GVL. Blood. 2010;115:122-132.
  13. Dodiuk-Gad RP, Olteanu C, Jeschke MG, et al. Treatment of toxic epidermal necrolysis in North America. J Am Acad Dermatol. 2015;73:876-877.
  14. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
References
  1. Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15:1555-1562.
  2. Jeanmonod P, Hubbuch M, Grünhage F, et al. Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation. Transpl Infect Dis. 2012;14:422-426.
  3. Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71:278-283.
  4. Scott-Lang V, Tidman M, McKay D. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31:532-534.
  5. Kingpin T, Mahasirimongkol S, Konyoung P, et al. Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics. 2015;25:402-411.
  6. Correia O, Delgado L, Barbosa IL, et al. Increased interleukin 10, tumor necrosis factor alpha, and interleukin 6 levels in blister fluid of toxic epidermal necrolysis. J Am Acad Dermatol. 2002;47:58-62.
  7. French LE, Tschopp J. Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition. Schweiz Med Wochenschr. 2000;130:1656-1661.
  8. Downey A, Jackson C, Harun N, et al. Toxic epidermal necrolysis: review of pathogenesis and management. J Am Acad Dermatol. 2012;66:995-1003.
  9. de Araujo E, Dessirier V, Laprée G, et al. Death ligand TRAIL, secreted by CD1a+ and CD14+ cells in blister fluids, is involved in killing keratinocytes in toxic epidermal necrolysis. Exp Dermatol. 2011;20:107-112.
  10. Viard-Leveugle I, Gaide O, Jankovic D, et al. TNF-α and IFN-γ are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol. 2013;133:489-498.
  11. Choi SW, Levine JE, Ferrara JL. Pathogenesis and management of graft-versus-host disease. Immunol Allergy Clin North Am. 2010;30:75-101.
  12. Markey KA, Burman AC, Banovic T, et al. Soluble lymphotoxin is an important effector molecule in GVHD and GVL. Blood. 2010;115:122-132.
  13. Dodiuk-Gad RP, Olteanu C, Jeschke MG, et al. Treatment of toxic epidermal necrolysis in North America. J Am Acad Dermatol. 2015;73:876-877.
  14. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
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  • Graft-vs-host disease (GVHD) and toxic epidermal necrolysis (TEN) are rare life-threatening complications seen in patients with allogeneic hematopoietic stem cell transplantation.
  • Although mild acute GVHD easily is distinguished from TEN, severe acute GVHD and TEN share overlapping features and present a diagnostic challenge.
  • Therapeutic decisions and associated outcomes hinge on accurate diagnosis, as high-dose systemic corticosteroids have been associated with higher mortality rates in TEN.
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Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations

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Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations
In Collaboration with the Skin of Color Society

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.1 However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.2 Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.4 Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.15 Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.1

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.16 This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.17 Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.1 Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Data collection flowchart of the total number of articles yielded in the literature search.

Results

Robinson et al18 conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ2=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.18

Hernandez et al19 used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.18 Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,19 similar to the Robinson et al18 study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al17 employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.17

A study by Chapman et al20 examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.20

 

 

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al18 study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al17 used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.21

In contrast to the Robinson et al18 study and Hernandez et al19 study, the Kundu et al17 study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.17

The Hernandez et al19 study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al18 and the 20-minute intervention used by Kundu et al.17 Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al19 study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al18 and Kundu et al17 studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al19 study. The 8-hour intervention in the Chapman et al20 study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.17 By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.22 In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.23 Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.24 Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.25 Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.26 Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

 

 

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

References
  1. Agbai ON, Buster K, Sanchez M, et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol. 2014;70:748-762.
  2. Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907-1914.
  3. Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
  4. Dawes SM, Tsai S, Gittleman H, et al. Racial disparities in melanoma survival. J Am Acad Dermatol. 2016;75:983-991.
  5. Byrd KM, Wilson DC, Hoyler SS, et al. Advanced presentation of melanoma in African Americans. J Am Acad Dermatol. 2004;50:21-24.
  6. Hu S, Parmet Y, Allen G, et al. Disparity in melanoma: a trend analysis of melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida. Arch Dermatol. 2009;145:1369-1374.
  7. Wu XC, Eide MJ, King J, et al. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006. J Am Acad Dermatol. 2011;65(5, suppl 1):S26-S37.
  8. Byrd-Miles K, Toombs EL, Peck GL. Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians. J Drugs Dermatol. 2007;6:10-16.
  9. Hu S, Soza-Vento RM, Parker DF, et al. Comparison of stage at diagnosis of melanoma among Hispanic, black, and white patients in Miami-Dade County, Florida. Arch Dermatol. 2006;142:704-708.
  10. Hu S, Parker DF, Thomas AG, et al. Advanced presentation of melanoma in African Americans: the Miami-Dade County experience. J Am Acad Dermatol. 2004;5:1031-1032.
  11. Bellows CF, Belafsky P, Fortgang IS, et al. Melanoma in African-Americans: trends in biological behavior and clinical characteristics over two decades. J Surg Oncol. 2001;78:10-16.
  12. Pritchett EN, Doyle A, Shaver CM, et al. Nonmelanoma skin cancer in nonwhite organ transplant recipients. JAMA Dermatol. 2016;152:1348-1353.
  13. Shin S, Palis BE, Phillips JL, et al. Cutaneous melanoma in Asian-Americans. J Surg Oncol. 2009;99:114-118.
  14. Stubblefield J, Kelly B. Melanoma in non-caucasian populations. Surg Clin North Am. 2014;94:1115-1126.
  15. Bradford PT, Goldstein AM, McMaster ML, et al. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145:427-434.
  16. Pichon LC, Corral I, Landrine H, et al. Perceived skin cancer risk and sunscreen use among African American adults. J Health Psychol. 2010;15:1181-1189.
  17. Kundu RV, Kamaria M, Ortiz S, et al. Effectiveness of a knowledge-based intervention for melanoma among those with ethnic skin. J Am Acad Dermatol. 2010;62:777-784.
  18. Robinson JK, Joshi KM, Ortiz S, et al. Melanoma knowledge, perception, and awareness in ethnic minorities in Chicago: recommendations regarding education. Psychooncology. 2010;20:313-320.
  19. Hernandez C, Wang S, Abraham I, et al. Evaluation of educational videos to increase skin cancer risk awareness and sun safe behaviors among adult Hispanics. J Cancer Educ. 2014;29:563-569.
  20. Chapman LW, Ochoa A, Tenconi F, et al. Dermatologic health literacy in underserved communities: a case report of south Los Angeles middle schools. Dermatol Online J. 2015;21. pii:13030/qt8671p40n.
  21. Yanina G, Gaber R, Clayman ML, et al. Sun protection education for diverse audiences: need for skin cancer pictures. J Cancer Educ. 2015;30:187-189.
  22. Dobbinson SJ, Volkov A, Wakefield MA. Continued impact of sunsmart advertising on youth and adults’ behaviors. Am J Prev Med. 2015;49:20-28.
  23. Rodrigues MA, Ross AL, Gilmore S, et al. Australian dermatologists’ perspective on skin of colour: results of a national survey [published online December 9, 2016]. Australas J Dermatol. doi:10.1111/ajd.12556.
  24. Jacobsen A, Galvan A, Lachapelle CC, et al. Defining the need for skin cancer prevention education in uninsured, minority, and immigrant communities. JAMA Dermatol. 2016;152:1342-1347.
  25. Hernandez C, Kim H, Mauleon G, et al. A pilot program in collaboration with community centers to increase awareness and participation in skin cancer screening among Latinos in Chicago. J Cancer Educ. 2013;28:342-345.
  26. Kailas A, Solomon JA, Mostow EN, et al. Gaps in the understanding and treatment of skin cancer in people of color. J Am Acad Dermatol. 2016;74:144-149.
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Mr. Kailas and Mr. Botwin are from the University of Central Florida College of Medicine, Orlando. Drs. Pritchett and Jackson-Richards are from the Multicultural Dermatology Center, Henry Ford Medical Center, Detroit, Michigan. Drs. Lewis and Sadhwani are from the Department of Dermatology, University of South Florida, Tampa. Dr. Desai is from the Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. Dr. Taylor is from the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Ajay Kailas, BS, UCF College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827 (ajay.kailas@knights.ucf.edu).

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Mr. Kailas and Mr. Botwin are from the University of Central Florida College of Medicine, Orlando. Drs. Pritchett and Jackson-Richards are from the Multicultural Dermatology Center, Henry Ford Medical Center, Detroit, Michigan. Drs. Lewis and Sadhwani are from the Department of Dermatology, University of South Florida, Tampa. Dr. Desai is from the Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. Dr. Taylor is from the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Ajay Kailas, BS, UCF College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827 (ajay.kailas@knights.ucf.edu).

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Mr. Kailas and Mr. Botwin are from the University of Central Florida College of Medicine, Orlando. Drs. Pritchett and Jackson-Richards are from the Multicultural Dermatology Center, Henry Ford Medical Center, Detroit, Michigan. Drs. Lewis and Sadhwani are from the Department of Dermatology, University of South Florida, Tampa. Dr. Desai is from the Department of Dermatology, University of Texas Southwestern Medical Center, Dallas. Dr. Taylor is from the Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

The authors report no conflict of interest.

Correspondence: Ajay Kailas, BS, UCF College of Medicine, 6850 Lake Nona Blvd, Orlando, FL 32827 (ajay.kailas@knights.ucf.edu).

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In Collaboration with the Skin of Color Society
In Collaboration with the Skin of Color Society

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.1 However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.2 Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.4 Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.15 Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.1

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.16 This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.17 Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.1 Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Data collection flowchart of the total number of articles yielded in the literature search.

Results

Robinson et al18 conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ2=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.18

Hernandez et al19 used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.18 Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,19 similar to the Robinson et al18 study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al17 employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.17

A study by Chapman et al20 examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.20

 

 

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al18 study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al17 used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.21

In contrast to the Robinson et al18 study and Hernandez et al19 study, the Kundu et al17 study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.17

The Hernandez et al19 study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al18 and the 20-minute intervention used by Kundu et al.17 Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al19 study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al18 and Kundu et al17 studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al19 study. The 8-hour intervention in the Chapman et al20 study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.17 By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.22 In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.23 Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.24 Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.25 Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.26 Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

 

 

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

Malignant melanoma, basal cell carcinoma, and squamous cell carcinoma account for approximately 40% of all neoplasms among the white population in the United States. Skin cancer is the most common malignancy in the United States.1 However, despite this occurrence, there are limited data regarding skin cancer in individuals with skin of color (SOC). The 5-year survival rates for melanoma are 58.2% for black individuals, 69.7% for Hispanics, and 70.9% for Asians compared to 79.8% for white individuals in the United States.2 Even though SOC populations have lower incidences of skin cancer—melanoma, basal cell carcinoma, and squamous cell carcinoma—they exhibit higher death rates.3-7 Nonetheless, no specific guidelines exist to address sun exposure and safety habits in SOC populations.6,8 Furthermore, current demographics suggest that by the year 2050, approximately half of the US population will be nonwhite.4 Paradoxically, despite having increased sun protection from greater amounts of melanin in their skin, black individuals are more likely to present with advanced-stage melanoma (eg, stage III/IV) compared to white individuals.8-12 Furthermore, those of nonwhite populations are more likely to present with more advanced stages of acral lentiginous melanomas than white individuals.13,14 Hispanics also face an increasing incidence of more invasive acral lentiginous melanomas.15 Overall, SOC patients have the poorest skin cancer prognosis, and the data suggest that the reason for this paradox is delayed diagnosis.1

Although skin cancer is largely a preventable condition, the literature suggests that lack of awareness of melanoma among ethnic minorities is one of the main reasons for their poor skin cancer prognosis.16 This lack of awareness decreases the likelihood that an SOC patient would be alert to early detection of cancerous changes.17 Because educating at-risk SOC populations is key to decreasing skin cancer risk, this study focused on determining the efficacy of major knowledge-based interventions conducted to date.1 Overall, we sought to answer the question, do knowledge-based interventions increase skin cancer awareness, knowledge, and protective behavior among people of color?

Methods

For this review, the Cochrane method of analysis was used to conduct a thorough search of PubMed articles indexed for MEDLINE (1994-2016), as well as a search of CINAHL (1997-2016), PsycINFO (1999-2016), and Web of Science (1965-2016), using a combination of more than 100 search terms including but not limited to skin cancer, skin of color, intervention, and ethnic skin. The search yielded a total of 52 articles (Figure). Following review, only 8 articles met inclusion criteria, which were as follows: (1) study was related to skin cancer in SOC patients, which included an intervention to increase skin cancer awareness and knowledge; (2) study included adult participants or adolescents aged 12 to 18 years; (3) study was written in English; and (4) study was published in a peer-reviewed journal. Of the remaining 8 articles, 4 were excluded due to the following criteria: (1) study failed to provide both preintervention and postintervention data, (2) study failed to provide quantitative data, and (3) study included participants who worked as health care professionals or ancillary staff. As a result, a total of 4 articles were analyzed and discussed in this review (Table).

Data collection flowchart of the total number of articles yielded in the literature search.

Results

Robinson et al18 conducted 12 focus groups with 120 total participants (40 black, 40 Asian, and 40 Hispanic patients). Participants engaged in a 2-hour tape-recorded focus group with a moderator guide on melanoma and skin cancer. Furthermore, they also were asked to assess skin cancer risk in 5 celebrities with different skin tones. The statistically significant preintervention results of the study (χ2=4.6, P<.001) were as follows: only 2%, 4%, and 14% correctly reported that celebrities with a very fair skin type, a fair skin type, and very dark skin type, respectively, could get sunburn, compared to 75%, 76%, and 62% post-intervention. Additionally, prior to intervention, 14% of the study population believed that dark brown skin type could get sunburn compared to 62% of the same group postintervention. This study demonstrated that the intervention helped SOC patients better identify their ability to get sunburn and identify their skin cancer risk.18

Hernandez et al19 used a video-based intervention in a Hispanic community, which was in contrast to the multiracial focus group intervention conducted by Robinson et al.18 Eighty Hispanic individuals were recruited from beauty salons to participate in the study. Participants watched two 3-minute videos in Spanish and completed a preintervention and postintervention survey. The first video emphasized the photoaging benefits of sun protection, while the second focused on skin cancer prevention. Preintervention surveys indicated that only 54 (68%) participants believed that fair-skinned Hispanics were at risk for skin cancer, which improved to 72 (90%) participants postintervention. Furthermore, initially only 44 (55%) participants thought those with darker skin types could develop skin cancer, but this number increased to 69 (86%) postintervention. For both questions regarding fair and dark skin, the agreement proportion was significantly different between the preeducation and posteducation videos (P<.0002 for the fair skin question and P<.0001 for the dark skin question). This study greatly increased awareness of skin cancer risk among Hispanics,19 similar to the Robinson et al18 study.

In contrast to 2-hour focus groups or 3-minute video–based interventions, a study by Kundu et al17 employed a 20-minute educational class-based intervention with both verbal and visual instruction. This study assessed the efficacy of an educational tutorial on improving awareness and early detection of melanoma in SOC individuals. Photographs were used to help participants recognize the ABCDEs of melanoma and to show examples of acral lentiginous melanomas in white individuals. A total of 71 participants completed a preintervention questionnaire, participated in a 20-minute class, and completed a postintervention questionnaire immediately after and 3 months following the class. The study population included 44 black, 15 Asian, 10 Hispanic, and 2 multiethnic participants. Knowledge that melanoma is a skin cancer increased from 83.9% to 100% immediately postintervention (P=.0001) and 97.2% at 3 months postintervention (P=.0075). Additionally, knowledge that people of color are at risk for melanoma increased from 48.4% preintervention to 82.8% immediately postintervention (P<.0001). However, only 40.8% of participants retained this knowledge at 3 months postintervention. Because only 1 participant reported a family history of skin cancer, the authors hypothesized that the reason for this loss of knowledge was that most participants were not personally affected by friends or family members with melanoma. A future study with an appropriate control group would be needed to support this claim. This study shed light on the potential of class-based interventions to increase both awareness and knowledge of skin cancer in SOC populations.17

A study by Chapman et al20 examined the effects of a sun protection educational program on increasing awareness of skin cancer in Hispanic and black middle school students in southern Los Angeles, California. It was the only study we reviewed that focused primarily on adolescents. Furthermore, it included the largest sample size (N=148) analyzed here. Students were given a preintervention questionnaire to evaluate their awareness of skin cancer and current sun-protection practices. Based on these results, the investigators devised a set of learning goals and incorporated them into an educational pamphlet. The intervention, called “Skin Teaching Day,” was a 1-day program discussing skin cancer and the importance of sun protection. Prior to the intervention, 68% of participants reported that they used sunscreen. Three months after completing the program, 80% of participants reported sunscreen use, an increase of 12% prior to the intervention. The results of this study demonstrated the unique effectiveness and potential of pamphlets in increasing sunscreen use.20

 

 

Comment

Overall, various methods of interventions such as focus groups, videos, pamphlets, and lectures improved knowledge of skin cancer risk and sun-protection behaviors in SOC populations. Furthermore, the unique differences of each study provided important insights into the successful design of an intervention.

An important characteristic of the Robinson et al18 study was the addition of photographs, which allowed participants not only to visualize different skin tones but also provided them with the opportunity to relate themselves to the photographs; by doing so, participants could effectively pick out the skin tone that best suited them. Written SOC scales are limited to mere descriptions and thus make it more difficult for participants to accurately identify the tone that best fits them. Kundu et al17 used photographs to teach skin self-examination and ABCDEs for detection of melanoma. Additionally, both studies used photographs to demonstrate examples of skin cancer.17,18 Recent evidence suggests the use of visuals can be efficacious for improving skin cancer knowledge and awareness; a study in 16 SOC kidney transplant recipients found that the addition of photographs of squamous cell carcinoma in various skin tones to a sun-protection educational pamphlet was more effective than the original pamphlet without photographs.21

In contrast to the Robinson et al18 study and Hernandez et al19 study, the Kundu et al17 study showed photographs of acral lentiginous melanomas in white patients rather than SOC patients. However, SOC populations may be less likely to relate to or identify skin changes in skin types that are different from their own. This technique was still beneficial, as acral lentiginous melanoma is the most common type of melanoma in SOC populations. Another benefit of the study was that it was the only study reviewed that included a follow-up postintervention questionnaire. Such data is useful, as it demonstrates how muchinformation is retained by participants and may be more likely to predict compliance with skin cancer protective behaviors.17

The Hernandez et al19 study is unique in that it was the only one to include an educational intervention entirely in Spanish, which is important to consider, as language may be a hindrance to participants’ understanding in the other studies, particularly Hispanics, possibly leading to a lack of information retention regarding sun-protective behaviors. Furthermore, it also was the only study to utilize videos as a method for interventions. The 3-minute videos demonstrated that interventions could be efficient as compared to the 2-hour in-class intervention used by Robinson et al18 and the 20-minute intervention used by Kundu et al.17 Additionally, videos also could be more cost-effective, as incentives for large focus groups would no longer be needed. Furthermore, in the Hernandez et al19 study, there was minimal to no disruption in the participants’ daily routine, as the participants were getting cosmetic services while watching the videos, perhaps allowing them to be more attentive. In contrast, both the Robinson et al18 and Kundu et al17 studies required time out from the participants’ daily schedules. In addition, these studies were notably longer than the Hernandez et al19 study. The 8-hour intervention in the Chapman et al20 study also may not be feasible for the general population because of its excessive length. However, the intervention was successful among the adolescent participants, which suggested that shorter durations are effective in the adult population and longer interventions may be more appropriate for adolescents because they benefit from peer activity.

Despite the success of the educational interventions as outlined in the 4 studies described here, a major epidemiologic flaw is that these interventions included only a small percentage of the target population. The largest total number of adults surveyed and undergoing an intervention in any of the populations was only 120.17 By failing to reach a substantial proportion of the population at risk, the number of preventable deaths likely will not decrease. The authors believe a larger-scale intervention would provide meaningful change. Australia’s SunSmart campaign to increase skin cancer awareness in the Australian population is an example of one such large-scale national intervention. The campaign focused on massive television advertisements in the summer to educate participants about the dangers of skin cancer and the importance of protective behaviors. Telephone surveys conducted from 1987 to 2011 demonstrated that more exposure to the advertisements in the SunSmart campaign meant that individuals were more likely to use sunscreen and avoid sun exposure.22 In the United States, a similar intervention would be of great benefit in educating SOC populations regarding skin cancer risk. Additionally, dermatology residents need to be adequately trained to educate patients of color about the risk for skin cancer, as survey data indicated more than 80% of Australian dermatologists desired more SOC teaching during their training and 50% indicated that they would have time to learn it during their training if offered.23 Furthermore, one study suggested that future interventions must include primary-, secondary-, and tertiary-prevention methods to effectively reduce skin cancer risk among patients of color.24 Primary prevention involves sun avoidance, secondary prevention involves detecting cancerous lesions, and tertiary prevention involves undergoing treatment of skin malignancies. However, increased knowledge does not necessarily mean increased preventative action will be employed (eg, sunscreen use, wearing sun-protective clothing and sunglasses, avoiding tanning beds and excessive sun exposure). Additional studies that demonstrate a notable increase in sun-protective behaviors related to increased knowledge are needed.

Because retention of skin cancer knowledge decreased in several postintervention surveys, there also is a dire need for continuing skin cancer education in patients of color, which may be accomplished through a combination effort of television advertisement campaigns, pamphlets, social media, community health departments, or even community members. For example, a pilot program found that Hispanic lay health workers who are educated about skin cancer may serve as a bridge between medical providers and the Hispanic community by encouraging individuals in this population to get regular skin examinations from a physician.25 Overall, there are currently gaps in the understanding and treatment of skin cancer in people of color.26 Identifying the advantages and disadvantages of all relevant skin cancer interventions conducted in the SOC population will hopefully guide future studies to help close these gaps by allowing others to design the best possible intervention. By doing so, researchers can generate an intervention that is precise, well-informed, and effective in decreasing mortality rates from skin cancer among SOC populations.

 

 

Conclusion

All of the studies reviewed demonstrated that instructional and educational interventions are promising methods for improving either knowledge, awareness, or safe skin practices and sun-protective behaviors in SOC populations to differing degrees (Table). Although each of the 4 interventions employed their own methods, they all increased 1 or more of the 3 aforementioned concepts—knowledge, awareness, or safe skin practices and sun-protective behaviors—when comparing postsurvey to presurvey data. However, the critically important message derived from this research is that there is a tremendous need for a substantial large-scale educational intervention to increase knowledge regarding skin cancer in SOC populations.

References
  1. Agbai ON, Buster K, Sanchez M, et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol. 2014;70:748-762.
  2. Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907-1914.
  3. Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
  4. Dawes SM, Tsai S, Gittleman H, et al. Racial disparities in melanoma survival. J Am Acad Dermatol. 2016;75:983-991.
  5. Byrd KM, Wilson DC, Hoyler SS, et al. Advanced presentation of melanoma in African Americans. J Am Acad Dermatol. 2004;50:21-24.
  6. Hu S, Parmet Y, Allen G, et al. Disparity in melanoma: a trend analysis of melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida. Arch Dermatol. 2009;145:1369-1374.
  7. Wu XC, Eide MJ, King J, et al. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006. J Am Acad Dermatol. 2011;65(5, suppl 1):S26-S37.
  8. Byrd-Miles K, Toombs EL, Peck GL. Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians. J Drugs Dermatol. 2007;6:10-16.
  9. Hu S, Soza-Vento RM, Parker DF, et al. Comparison of stage at diagnosis of melanoma among Hispanic, black, and white patients in Miami-Dade County, Florida. Arch Dermatol. 2006;142:704-708.
  10. Hu S, Parker DF, Thomas AG, et al. Advanced presentation of melanoma in African Americans: the Miami-Dade County experience. J Am Acad Dermatol. 2004;5:1031-1032.
  11. Bellows CF, Belafsky P, Fortgang IS, et al. Melanoma in African-Americans: trends in biological behavior and clinical characteristics over two decades. J Surg Oncol. 2001;78:10-16.
  12. Pritchett EN, Doyle A, Shaver CM, et al. Nonmelanoma skin cancer in nonwhite organ transplant recipients. JAMA Dermatol. 2016;152:1348-1353.
  13. Shin S, Palis BE, Phillips JL, et al. Cutaneous melanoma in Asian-Americans. J Surg Oncol. 2009;99:114-118.
  14. Stubblefield J, Kelly B. Melanoma in non-caucasian populations. Surg Clin North Am. 2014;94:1115-1126.
  15. Bradford PT, Goldstein AM, McMaster ML, et al. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145:427-434.
  16. Pichon LC, Corral I, Landrine H, et al. Perceived skin cancer risk and sunscreen use among African American adults. J Health Psychol. 2010;15:1181-1189.
  17. Kundu RV, Kamaria M, Ortiz S, et al. Effectiveness of a knowledge-based intervention for melanoma among those with ethnic skin. J Am Acad Dermatol. 2010;62:777-784.
  18. Robinson JK, Joshi KM, Ortiz S, et al. Melanoma knowledge, perception, and awareness in ethnic minorities in Chicago: recommendations regarding education. Psychooncology. 2010;20:313-320.
  19. Hernandez C, Wang S, Abraham I, et al. Evaluation of educational videos to increase skin cancer risk awareness and sun safe behaviors among adult Hispanics. J Cancer Educ. 2014;29:563-569.
  20. Chapman LW, Ochoa A, Tenconi F, et al. Dermatologic health literacy in underserved communities: a case report of south Los Angeles middle schools. Dermatol Online J. 2015;21. pii:13030/qt8671p40n.
  21. Yanina G, Gaber R, Clayman ML, et al. Sun protection education for diverse audiences: need for skin cancer pictures. J Cancer Educ. 2015;30:187-189.
  22. Dobbinson SJ, Volkov A, Wakefield MA. Continued impact of sunsmart advertising on youth and adults’ behaviors. Am J Prev Med. 2015;49:20-28.
  23. Rodrigues MA, Ross AL, Gilmore S, et al. Australian dermatologists’ perspective on skin of colour: results of a national survey [published online December 9, 2016]. Australas J Dermatol. doi:10.1111/ajd.12556.
  24. Jacobsen A, Galvan A, Lachapelle CC, et al. Defining the need for skin cancer prevention education in uninsured, minority, and immigrant communities. JAMA Dermatol. 2016;152:1342-1347.
  25. Hernandez C, Kim H, Mauleon G, et al. A pilot program in collaboration with community centers to increase awareness and participation in skin cancer screening among Latinos in Chicago. J Cancer Educ. 2013;28:342-345.
  26. Kailas A, Solomon JA, Mostow EN, et al. Gaps in the understanding and treatment of skin cancer in people of color. J Am Acad Dermatol. 2016;74:144-149.
References
  1. Agbai ON, Buster K, Sanchez M, et al. Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public. J Am Acad Dermatol. 2014;70:748-762.
  2. Cormier JN, Xing Y, Ding M, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907-1914.
  3. Gloster HM Jr, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006;55:741-760.
  4. Dawes SM, Tsai S, Gittleman H, et al. Racial disparities in melanoma survival. J Am Acad Dermatol. 2016;75:983-991.
  5. Byrd KM, Wilson DC, Hoyler SS, et al. Advanced presentation of melanoma in African Americans. J Am Acad Dermatol. 2004;50:21-24.
  6. Hu S, Parmet Y, Allen G, et al. Disparity in melanoma: a trend analysis of melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida. Arch Dermatol. 2009;145:1369-1374.
  7. Wu XC, Eide MJ, King J, et al. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006. J Am Acad Dermatol. 2011;65(5, suppl 1):S26-S37.
  8. Byrd-Miles K, Toombs EL, Peck GL. Skin cancer in individuals of African, Asian, Latin-American, and American-Indian descent: differences in incidence, clinical presentation, and survival compared to Caucasians. J Drugs Dermatol. 2007;6:10-16.
  9. Hu S, Soza-Vento RM, Parker DF, et al. Comparison of stage at diagnosis of melanoma among Hispanic, black, and white patients in Miami-Dade County, Florida. Arch Dermatol. 2006;142:704-708.
  10. Hu S, Parker DF, Thomas AG, et al. Advanced presentation of melanoma in African Americans: the Miami-Dade County experience. J Am Acad Dermatol. 2004;5:1031-1032.
  11. Bellows CF, Belafsky P, Fortgang IS, et al. Melanoma in African-Americans: trends in biological behavior and clinical characteristics over two decades. J Surg Oncol. 2001;78:10-16.
  12. Pritchett EN, Doyle A, Shaver CM, et al. Nonmelanoma skin cancer in nonwhite organ transplant recipients. JAMA Dermatol. 2016;152:1348-1353.
  13. Shin S, Palis BE, Phillips JL, et al. Cutaneous melanoma in Asian-Americans. J Surg Oncol. 2009;99:114-118.
  14. Stubblefield J, Kelly B. Melanoma in non-caucasian populations. Surg Clin North Am. 2014;94:1115-1126.
  15. Bradford PT, Goldstein AM, McMaster ML, et al. Acral lentiginous melanoma: incidence and survival patterns in the United States, 1986-2005. Arch Dermatol. 2009;145:427-434.
  16. Pichon LC, Corral I, Landrine H, et al. Perceived skin cancer risk and sunscreen use among African American adults. J Health Psychol. 2010;15:1181-1189.
  17. Kundu RV, Kamaria M, Ortiz S, et al. Effectiveness of a knowledge-based intervention for melanoma among those with ethnic skin. J Am Acad Dermatol. 2010;62:777-784.
  18. Robinson JK, Joshi KM, Ortiz S, et al. Melanoma knowledge, perception, and awareness in ethnic minorities in Chicago: recommendations regarding education. Psychooncology. 2010;20:313-320.
  19. Hernandez C, Wang S, Abraham I, et al. Evaluation of educational videos to increase skin cancer risk awareness and sun safe behaviors among adult Hispanics. J Cancer Educ. 2014;29:563-569.
  20. Chapman LW, Ochoa A, Tenconi F, et al. Dermatologic health literacy in underserved communities: a case report of south Los Angeles middle schools. Dermatol Online J. 2015;21. pii:13030/qt8671p40n.
  21. Yanina G, Gaber R, Clayman ML, et al. Sun protection education for diverse audiences: need for skin cancer pictures. J Cancer Educ. 2015;30:187-189.
  22. Dobbinson SJ, Volkov A, Wakefield MA. Continued impact of sunsmart advertising on youth and adults’ behaviors. Am J Prev Med. 2015;49:20-28.
  23. Rodrigues MA, Ross AL, Gilmore S, et al. Australian dermatologists’ perspective on skin of colour: results of a national survey [published online December 9, 2016]. Australas J Dermatol. doi:10.1111/ajd.12556.
  24. Jacobsen A, Galvan A, Lachapelle CC, et al. Defining the need for skin cancer prevention education in uninsured, minority, and immigrant communities. JAMA Dermatol. 2016;152:1342-1347.
  25. Hernandez C, Kim H, Mauleon G, et al. A pilot program in collaboration with community centers to increase awareness and participation in skin cancer screening among Latinos in Chicago. J Cancer Educ. 2013;28:342-345.
  26. Kailas A, Solomon JA, Mostow EN, et al. Gaps in the understanding and treatment of skin cancer in people of color. J Am Acad Dermatol. 2016;74:144-149.
Issue
Cutis - 100(4)
Issue
Cutis - 100(4)
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235-240
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235-240
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Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations
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Assessing the Effectiveness of Knowledge-Based Interventions in Increasing Skin Cancer Awareness, Knowledge, and Protective Behaviors in Skin of Color Populations
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  • Patients of color should be informed that they are at risk for skin cancer including melanoma.
  • Patients of color should be taught to identify suspicious skin lesions including the ABCDEs of melanoma.
  • Patients of color should be instructed to perform self-body skin examinations, especially of the palms and soles, for any evolving skin lesions. Patients should be instructed on the importance of visiting a physician for an evolving or suspicious mole or lesion.
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