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Updates in Our Understanding of Central Centrifugal Cicatricial Alopecia
It has been more than 50 years since central centrifugal cicatricial alopecia (CCCA) was first defined by LoPresti and colleagues1 as hot comb alopecia. Fifty years later, we are only just starting to understand the pathogenesis of CCCA and its systemic implications.
Then and Now
The use of hot combs, a metal device used to straighten naturally curly hair, was ubiquitous in the households of black women in the 1960s. It is no surprise then that this styling process was labeled as the culprit of this disease that affects black women almost exclusively. As the use of hot combs waned but the prevalence of CCCA persisted, its name evolved to chemically induced alopecia—an ode to the popular styling product of the 1990s, the chemical relaxer—and eventually CCCA, a name that reflects its clinical progression and histologic findings.2
Since then, research has explored the association with systemic diseases, some noting increased rates of type 2 diabetes mellitus and thyroid disease, and more recently, an increased rate of fibroids in affected patients.3,4
Clues to Pathogenesis
Compared to other primary cicatricial alopecias, CCCA is unique in that active progression is difficult to detect. Symptoms, such as pruritus, often are minimal or absent, rendering clinical assessment quite difficult.5 Unlike other forms of scarring hair loss, fibrosis, not inflammation, is the predominant clinical feature. The clinical presentation is not unlike a group of disorders termed fibroproliferative disorders, which includes systemic sclerosis, uterine fibroids, atherosclerosis, and keloids, among others. It has been postulated that diseases of aberrant scarring are more common in black individuals due to the protective effect profibrotic alleles have against endemic helminthic infections of sub-Saharan infections, including oncocerciasis.6
A recent study showed an increased expression of fibroproliferative genes, particularly those implicated in other fibroproliferative disorders, in affected scalp of patients with CCCA.7 Most notably, an expression in gene overlap was noted between fibroids and CCCA in this study, though the relationship between these two diseases needs to be further explored.
Gene Variants Identified in CCCA
More recently, a new study has identified a gene variant of peptidyl arginine deiminase 3, PADI3, that is present in approximately one-quarter of studied patients with CCCA.8PADI3 plays a role in hair shaft formation and has been implicated in another hair disorder, uncombable hair syndrome, though the latter presents in children, improves with age, and is not associated with a scarring phenotype.9 However, this study has provided greater insight into our understanding of CCCA by establishing a possible genetic predisposition in patients affected with this disease.8
What’s Next for CCCA?
For years, many patients with CCCA have been turned away with few answers and left thinking that it is their own styling habits that have led to their hair loss,
The future is bright for CCCA. Although our understanding of CCCA is still in its infancy, it is my hope that with greater understanding of this disease will come greater empathy for our patients.
- LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol. 1968;98:234-238.
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668.
- Kyei A, Bergfeld WF, Piliang M, et al. Medical and environmental risk factors for the development of central centrifugal cicatricial alopecia: a population study. Arch Dermatol. 2011;147:909-914.
- Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with central centrifugal cicatricial alopecia. JAMA Dermatol. 2018;154:213-214.
- Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther. 2008;21:268-278.
- Hellwege JN, Torstenson ES, Russell SB, et al. Evidence of selection as a cause for racial disparities in fibroproliferative disease. PLoS One. 2017;12:e0182791. doi:10.1371/journal.pone.0182791.
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904.e1-912.e1.
- Malki L, Sarig O, Romano MT, et al. Variant PADI3 in central centrifugal cicatricial alopecia. N Engl J Med. 2019;380:833-841.
- Matis WL, Baden H, Green R, et al. Uncombable-hair syndrome. Pediatr Dermatol. 1987;4:215-219.
It has been more than 50 years since central centrifugal cicatricial alopecia (CCCA) was first defined by LoPresti and colleagues1 as hot comb alopecia. Fifty years later, we are only just starting to understand the pathogenesis of CCCA and its systemic implications.
Then and Now
The use of hot combs, a metal device used to straighten naturally curly hair, was ubiquitous in the households of black women in the 1960s. It is no surprise then that this styling process was labeled as the culprit of this disease that affects black women almost exclusively. As the use of hot combs waned but the prevalence of CCCA persisted, its name evolved to chemically induced alopecia—an ode to the popular styling product of the 1990s, the chemical relaxer—and eventually CCCA, a name that reflects its clinical progression and histologic findings.2
Since then, research has explored the association with systemic diseases, some noting increased rates of type 2 diabetes mellitus and thyroid disease, and more recently, an increased rate of fibroids in affected patients.3,4
Clues to Pathogenesis
Compared to other primary cicatricial alopecias, CCCA is unique in that active progression is difficult to detect. Symptoms, such as pruritus, often are minimal or absent, rendering clinical assessment quite difficult.5 Unlike other forms of scarring hair loss, fibrosis, not inflammation, is the predominant clinical feature. The clinical presentation is not unlike a group of disorders termed fibroproliferative disorders, which includes systemic sclerosis, uterine fibroids, atherosclerosis, and keloids, among others. It has been postulated that diseases of aberrant scarring are more common in black individuals due to the protective effect profibrotic alleles have against endemic helminthic infections of sub-Saharan infections, including oncocerciasis.6
A recent study showed an increased expression of fibroproliferative genes, particularly those implicated in other fibroproliferative disorders, in affected scalp of patients with CCCA.7 Most notably, an expression in gene overlap was noted between fibroids and CCCA in this study, though the relationship between these two diseases needs to be further explored.
Gene Variants Identified in CCCA
More recently, a new study has identified a gene variant of peptidyl arginine deiminase 3, PADI3, that is present in approximately one-quarter of studied patients with CCCA.8PADI3 plays a role in hair shaft formation and has been implicated in another hair disorder, uncombable hair syndrome, though the latter presents in children, improves with age, and is not associated with a scarring phenotype.9 However, this study has provided greater insight into our understanding of CCCA by establishing a possible genetic predisposition in patients affected with this disease.8
What’s Next for CCCA?
For years, many patients with CCCA have been turned away with few answers and left thinking that it is their own styling habits that have led to their hair loss,
The future is bright for CCCA. Although our understanding of CCCA is still in its infancy, it is my hope that with greater understanding of this disease will come greater empathy for our patients.
It has been more than 50 years since central centrifugal cicatricial alopecia (CCCA) was first defined by LoPresti and colleagues1 as hot comb alopecia. Fifty years later, we are only just starting to understand the pathogenesis of CCCA and its systemic implications.
Then and Now
The use of hot combs, a metal device used to straighten naturally curly hair, was ubiquitous in the households of black women in the 1960s. It is no surprise then that this styling process was labeled as the culprit of this disease that affects black women almost exclusively. As the use of hot combs waned but the prevalence of CCCA persisted, its name evolved to chemically induced alopecia—an ode to the popular styling product of the 1990s, the chemical relaxer—and eventually CCCA, a name that reflects its clinical progression and histologic findings.2
Since then, research has explored the association with systemic diseases, some noting increased rates of type 2 diabetes mellitus and thyroid disease, and more recently, an increased rate of fibroids in affected patients.3,4
Clues to Pathogenesis
Compared to other primary cicatricial alopecias, CCCA is unique in that active progression is difficult to detect. Symptoms, such as pruritus, often are minimal or absent, rendering clinical assessment quite difficult.5 Unlike other forms of scarring hair loss, fibrosis, not inflammation, is the predominant clinical feature. The clinical presentation is not unlike a group of disorders termed fibroproliferative disorders, which includes systemic sclerosis, uterine fibroids, atherosclerosis, and keloids, among others. It has been postulated that diseases of aberrant scarring are more common in black individuals due to the protective effect profibrotic alleles have against endemic helminthic infections of sub-Saharan infections, including oncocerciasis.6
A recent study showed an increased expression of fibroproliferative genes, particularly those implicated in other fibroproliferative disorders, in affected scalp of patients with CCCA.7 Most notably, an expression in gene overlap was noted between fibroids and CCCA in this study, though the relationship between these two diseases needs to be further explored.
Gene Variants Identified in CCCA
More recently, a new study has identified a gene variant of peptidyl arginine deiminase 3, PADI3, that is present in approximately one-quarter of studied patients with CCCA.8PADI3 plays a role in hair shaft formation and has been implicated in another hair disorder, uncombable hair syndrome, though the latter presents in children, improves with age, and is not associated with a scarring phenotype.9 However, this study has provided greater insight into our understanding of CCCA by establishing a possible genetic predisposition in patients affected with this disease.8
What’s Next for CCCA?
For years, many patients with CCCA have been turned away with few answers and left thinking that it is their own styling habits that have led to their hair loss,
The future is bright for CCCA. Although our understanding of CCCA is still in its infancy, it is my hope that with greater understanding of this disease will come greater empathy for our patients.
- LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol. 1968;98:234-238.
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668.
- Kyei A, Bergfeld WF, Piliang M, et al. Medical and environmental risk factors for the development of central centrifugal cicatricial alopecia: a population study. Arch Dermatol. 2011;147:909-914.
- Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with central centrifugal cicatricial alopecia. JAMA Dermatol. 2018;154:213-214.
- Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther. 2008;21:268-278.
- Hellwege JN, Torstenson ES, Russell SB, et al. Evidence of selection as a cause for racial disparities in fibroproliferative disease. PLoS One. 2017;12:e0182791. doi:10.1371/journal.pone.0182791.
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904.e1-912.e1.
- Malki L, Sarig O, Romano MT, et al. Variant PADI3 in central centrifugal cicatricial alopecia. N Engl J Med. 2019;380:833-841.
- Matis WL, Baden H, Green R, et al. Uncombable-hair syndrome. Pediatr Dermatol. 1987;4:215-219.
- LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol. 1968;98:234-238.
- Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668.
- Kyei A, Bergfeld WF, Piliang M, et al. Medical and environmental risk factors for the development of central centrifugal cicatricial alopecia: a population study. Arch Dermatol. 2011;147:909-914.
- Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with central centrifugal cicatricial alopecia. JAMA Dermatol. 2018;154:213-214.
- Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther. 2008;21:268-278.
- Hellwege JN, Torstenson ES, Russell SB, et al. Evidence of selection as a cause for racial disparities in fibroproliferative disease. PLoS One. 2017;12:e0182791. doi:10.1371/journal.pone.0182791.
- Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904.e1-912.e1.
- Malki L, Sarig O, Romano MT, et al. Variant PADI3 in central centrifugal cicatricial alopecia. N Engl J Med. 2019;380:833-841.
- Matis WL, Baden H, Green R, et al. Uncombable-hair syndrome. Pediatr Dermatol. 1987;4:215-219.
