Rosacea is a common chronic inflammatory skin disorder of recurrent facial flushing of the central face that is estimated to affect 16 million Americans1,2; signs and symptoms typically first appear between 30 and 60 years of age. The disease consists of various combinations of primary and secondary signs and symptoms and varies from one patient to another, including flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and rhinophyma. It may include sensations of burning and stinging, as well as ocular symptoms of foreign-body sensation and dryness.3
The most common presentations of primary and secondary features have been designated as subtypes, and patients may have more than one subtype at a time. Subtype 1, erythematotelangiectatic rosacea, is characterized by flushing and persistent erythema on the central face without telangiectasia, edema, stinging, or roughness. Subtype 2, papulopustular rosacea, may consist of persistent erythema, papules, pustules, and burning/stinging. Subtype 3, phymatous rosacea, may include thickening skin, irregular nodularities, and enlargement, especially of the nose. Subtype 4, ocular rosacea, may comprise foreign-body sensation, burning/stinging, dryness, itching, photosensitivity, and blurred vision.3 Management options for rosacea include medical therapy, lifestyle modifications, and appropriate skin care.
Beyond its many potential physical effects, surveys by the National Rosacea Society (NRS) found rosacea can cause significant psychological, emotional, and occupational problems if left untreated.4 The pathogenesis of rosacea is unknown; however, new research has linked the disease to increased risk of various comorbidities.
This article looks at the prevalence of rosacea and highlights recent studies on the association between rosacea and other diseases and if the results are impacting how dermatologists diagnose, manage, and treat this cutaneous disorder.
Disease Prevalence
Only a small fraction of the 16 million individuals living with rosacea are seeking treatment, according to data from a large population study that showed an estimated 82% of individuals are currently untreated.5
“It is difficult to understand why so many people don’t seek treatment. They may think that they have adult acne and try to self-treat. They may be embarrassed to make an appointment and to talk to someone about their skin,” said Julie C. Harper, MD, who is in private practice at the Dermatology and Skin Care Center of Birmingham and clinical associate professor of dermatology at the University of Alabama at Birmingham, in an interview with The Dermatologist. “The lay population have long associated rosacea with alcohol consumption and they may feel shamed by that association even if they are nondrinkers. All of these things boil down to a lack of understanding and awareness of what rosacea is.”
Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center (Morristown, NJ) and clinical associate professor of dermatology at Rutgers University, who was also interviewed, agreed there is a lack of patient awareness. “I have seen people come into my office with relatively bad rosacea who are there to discuss another condition,” she said, noting that signs and symptoms of the disease may not bother patients, and they may not be aware they have a disease or that treatments are available.
Article continues on page 2
{{pagebreak}}
Rosacea and Comorbidities
Recent medical research has suggested that rosacea may also be associated with systemic diseases, neurologic diseases, certain types of cancer and more. A 2015 case-control study conducted by Rainer and colleagues6 at Johns Hopkins University of 130 individuals with rosacea found a significant association between rosacea and allergies, gastroesophageal reflux disease (GERD), other gastrointestinal (GI) diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance.
Additionally, moderate to severe rosacea was associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular disease and GERD.
“Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those presenting with more severe disease,” the researchers concluded.
Recent findings of large-scale studies of health data in Taiwan1 and from the Danish National Patient Registry7 have demonstrated potential associations between rosacea and inflammatory bowel disease (IBD) and GI disorders.
Wu and colleagues1 investigated the link between rosacea and IBD, including Crohn disease and ulcerative colitis, in a nationwide cohort study of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 who were identified in the Taiwanese National Health Insurance Research Database. The researchers also examined the effects of antibiotics.
The 15-year cumulative incidences of IBD showed a small increased risk in patients with rosacea (0.036; 95% CI, 0.00-1.5) compared with patients without the disease (0.019; 95% CI, 0.00-0.83). Rosacea (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.04-3.63) and male gender (aHR, 3.52; 95% CI, 2.03-6.11) were independently associated with IBD, after adjustment for major comorbidities. These results were consistent across different subgroups of patients on multivariate subgroup analyses.
A sensitivity analysis that examined the association between antibiotic treatment and subsequent IBD in patients with rosacea demonstrated that long-term frequent antibiotic users had lower incidence of IBD, but without statistical significance. The researchers noted that the link between long-term antibiotic use and the development of IBD warrants further investigation.
A separate study7 examined the link between rosacea and certain GI disorders, with a focus on celiac disease, Crohn disease, ulcerative colitis, Helicobactor pylori infection, small intestinal bacterial overgrowth (SIBO), and irritable bowel syndrome (IBS). The researchers selected these conditions due to their mechanistic and pathogenic overlap with rosacea.
As in their previous comorbidity studies, Egeberg and colleagues tracked more than 4.3 million individuals in the Danish National Patient Registry for 5 years, including 49,475 who were diagnosed with rosacea. The researchers found a higher prevalence of these 6 GI disorders among patients with rosacea compared with the control group. Adjusted HRs showed significant associations between rosacea and celiac disease (HR, 1.46; 95% CI, 1.11-1.93), Crohn disease (HR, 1.45; 95% CI, 1.19-1.77), ulcerative colitis (HR, 1.19; 95% CI, 1.02-1.39), and IBS (HR, 1.34; 95% CI, 1.19-1.50), but not H pylori infection (HR, 1.04; 95% CI, 0.96-1.13) or SIBO (HR, 0.71; 95% CI, 0.18-1.86). The researchers noted that further study is needed to determine potential common causal factors and examine the underlying mechanisms and clinical consequences of these associations.
Rosacea and the occurrence of cancer has also been investigated, but data is limited. In the ongoing Nurses’ Health Study II of more than 116,000 women who complete a biennial questionnaire on medical history and lifestyle practices, the more than 6,000 women with a diagnosis of rosacea were found to be 1.59 times more likely to have thyroid cancer and 1.5 times more likely to have basal cell carcinoma compared with those without rosacea.3,8
Because the potential link between rosacea and other cancers remains poorly investigated, Egeberg and colleagues9 recently examined that association between rosacea and selected cancers using health data from the Danish National Patient Registry. The researchers observed significant associations between rosacea and hepatic cancer (HR, 1.42; 95% CI, 1.06-1.90), nonmelanoma skin cancer (HR, 1.36; 95% CI, 1.26-1.47), and breast cancer (HR, 1.25; 95% CI, 1.15-1.36). Notably, the risk of lung cancer was significantly decreased among patients with rosacea (HR, 0.78; 95% CI, 0.69-0.89).
“These results are in contrast to the limited published data on cancers in rosacea, and further studies are warranted to elucidate the potential relationship between rosacea and various cancers,” concluded the researchers. “Potentially, factors such as skin color, alcohol intake, and tobacco use, which we were not able to control for in this report, may help explain some of these findings.”
Drs Harper and Baldwin, who are members of the NRS Medical Advisory Board, said they do not believe the recent surge of scientific studies showing a link between rosacea and various comorbidities has yet to impact how dermatologists diagnosis, manage, and treat rosacea.
“All of these studies are database studies that are able to show an association between the two conditions in question. These studies have my attention because of what they might teach us about the pathogenesis of rosacea and about inflammation in the skin and in the body in general,” said Dr Harper.
“If you have 16 million older people 40 to 60 years of age, it’s not surprising that a large number of them might have common medical conditions like GERD, IBD, Parkinson disease, and cardiovascular disease,” said Dr Baldwin. “We know that acne is associated with gastrointestinal problems. Psoriasis is associated with cardiovascular disease. It may be that inflammatory skin conditions are associated with inflammatory systemic conditions. If inflammation is the common connector, then the more inflamed you are, the more association there might be.” She suggested more attention to comorbidities may be appropriate for patients with more severe rosacea.
Article continues on page 3
{{pagebreak}}
Education Is Key
Dr Baldwin agreed that patient education about rosacea and its potential comorbidities is important. She said patients also need to be truthful about any symptoms they are experiencing when filling out patient health forms in the dermatology office and when seeing the dermatologist.
She also said that more education for dermatologists to recognize comorbidities associated with rosacea is warranted considering the amount of data being published. “I fear that these frequent articles [about rosacea and comorbidities] are numbing dermatologists to the real issue. There is a role for education in a rational and sensible way,” Dr Baldwin explained.
“The reason for education I think would be to tie together the various reported comorbidities and to focus in on a couple that make more medical sense and for which there is more medical data, such as gastrointestinal and cardiovascular disease,” she said.
To bring attention to the early warning signs of rosacea and encourage individuals who suspect they may have the disease to see a dermatologist for diagnosis and appropriate therapy, the NRS has designated April as Rosacea Awareness Month. Bulk quantities of educational materials are available to health care professionals for their patients through the NRS website.
The NRS offers Rosacea Review, a newsletter for patients; a “Rosacea Diary” to help patients identify and avoid lifestyle factors that may trigger flare-ups in their individual cases; and other booklets to help patients understand and manage their condition. For more information, visit the physicians section of the NRS website https://www.rosacea.org/physicians/.
References
1. Wu CY, Chang, YT, Juan CK. Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan [published online January 7, 2017]. J Am Acad Dermatol. doi:10.1016/j.jaad.2016.11.065
2. Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015;72(5):749-758.
3. Wolf JE Jr. Rosacea diagnosis and management. The Dermatologist. 2017;25(2):21-25.
4. What is rosacea. National Rosacea Society website. https://www.rosacea.org. Accessed March 28, 2017.
5. Wehausen B, Hill DE, Feldman SR. Most people with psoriasis or rosacea are not being treated: a large population study. Dermatol Online J. 2016;22(7). pii:13030/qt4nc3p4q2.
6. Rainer BM, Fischer AH, Luz Felipe da Silva D, Kang S, Chien AL. Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. J Am Acad Dermatol. 2015;73(4):604-608.
7. Egeberg A, Weinstock LB, Thyssen EP, Gislason GH, Thyssen JP. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017;176(1):100-106.
8. Li W-Q, Zhang M, Danby FW, Han J, Qureshi AA. Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer. 2015;113(3):520-523.
9. Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Rosacea and risk of cancer in Denmark. Cancer Epidemiol. 2017;47:76-80.
Rosacea is a common chronic inflammatory skin disorder of recurrent facial flushing of the central face that is estimated to affect 16 million Americans1,2; signs and symptoms typically first appear between 30 and 60 years of age. The disease consists of various combinations of primary and secondary signs and symptoms and varies from one patient to another, including flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and rhinophyma. It may include sensations of burning and stinging, as well as ocular symptoms of foreign-body sensation and dryness.3
The most common presentations of primary and secondary features have been designated as subtypes, and patients may have more than one subtype at a time. Subtype 1, erythematotelangiectatic rosacea, is characterized by flushing and persistent erythema on the central face without telangiectasia, edema, stinging, or roughness. Subtype 2, papulopustular rosacea, may consist of persistent erythema, papules, pustules, and burning/stinging. Subtype 3, phymatous rosacea, may include thickening skin, irregular nodularities, and enlargement, especially of the nose. Subtype 4, ocular rosacea, may comprise foreign-body sensation, burning/stinging, dryness, itching, photosensitivity, and blurred vision.3 Management options for rosacea include medical therapy, lifestyle modifications, and appropriate skin care.
Beyond its many potential physical effects, surveys by the National Rosacea Society (NRS) found rosacea can cause significant psychological, emotional, and occupational problems if left untreated.4 The pathogenesis of rosacea is unknown; however, new research has linked the disease to increased risk of various comorbidities.
This article looks at the prevalence of rosacea and highlights recent studies on the association between rosacea and other diseases and if the results are impacting how dermatologists diagnose, manage, and treat this cutaneous disorder.
Disease Prevalence
Only a small fraction of the 16 million individuals living with rosacea are seeking treatment, according to data from a large population study that showed an estimated 82% of individuals are currently untreated.5
“It is difficult to understand why so many people don’t seek treatment. They may think that they have adult acne and try to self-treat. They may be embarrassed to make an appointment and to talk to someone about their skin,” said Julie C. Harper, MD, who is in private practice at the Dermatology and Skin Care Center of Birmingham and clinical associate professor of dermatology at the University of Alabama at Birmingham, in an interview with The Dermatologist. “The lay population have long associated rosacea with alcohol consumption and they may feel shamed by that association even if they are nondrinkers. All of these things boil down to a lack of understanding and awareness of what rosacea is.”
Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center (Morristown, NJ) and clinical associate professor of dermatology at Rutgers University, who was also interviewed, agreed there is a lack of patient awareness. “I have seen people come into my office with relatively bad rosacea who are there to discuss another condition,” she said, noting that signs and symptoms of the disease may not bother patients, and they may not be aware they have a disease or that treatments are available.
Article continues on page 2
{{pagebreak}}
Rosacea and Comorbidities
Recent medical research has suggested that rosacea may also be associated with systemic diseases, neurologic diseases, certain types of cancer and more. A 2015 case-control study conducted by Rainer and colleagues6 at Johns Hopkins University of 130 individuals with rosacea found a significant association between rosacea and allergies, gastroesophageal reflux disease (GERD), other gastrointestinal (GI) diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance.
Additionally, moderate to severe rosacea was associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular disease and GERD.
“Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those presenting with more severe disease,” the researchers concluded.
Recent findings of large-scale studies of health data in Taiwan1 and from the Danish National Patient Registry7 have demonstrated potential associations between rosacea and inflammatory bowel disease (IBD) and GI disorders.
Wu and colleagues1 investigated the link between rosacea and IBD, including Crohn disease and ulcerative colitis, in a nationwide cohort study of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 who were identified in the Taiwanese National Health Insurance Research Database. The researchers also examined the effects of antibiotics.
The 15-year cumulative incidences of IBD showed a small increased risk in patients with rosacea (0.036; 95% CI, 0.00-1.5) compared with patients without the disease (0.019; 95% CI, 0.00-0.83). Rosacea (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.04-3.63) and male gender (aHR, 3.52; 95% CI, 2.03-6.11) were independently associated with IBD, after adjustment for major comorbidities. These results were consistent across different subgroups of patients on multivariate subgroup analyses.
A sensitivity analysis that examined the association between antibiotic treatment and subsequent IBD in patients with rosacea demonstrated that long-term frequent antibiotic users had lower incidence of IBD, but without statistical significance. The researchers noted that the link between long-term antibiotic use and the development of IBD warrants further investigation.
A separate study7 examined the link between rosacea and certain GI disorders, with a focus on celiac disease, Crohn disease, ulcerative colitis, Helicobactor pylori infection, small intestinal bacterial overgrowth (SIBO), and irritable bowel syndrome (IBS). The researchers selected these conditions due to their mechanistic and pathogenic overlap with rosacea.
As in their previous comorbidity studies, Egeberg and colleagues tracked more than 4.3 million individuals in the Danish National Patient Registry for 5 years, including 49,475 who were diagnosed with rosacea. The researchers found a higher prevalence of these 6 GI disorders among patients with rosacea compared with the control group. Adjusted HRs showed significant associations between rosacea and celiac disease (HR, 1.46; 95% CI, 1.11-1.93), Crohn disease (HR, 1.45; 95% CI, 1.19-1.77), ulcerative colitis (HR, 1.19; 95% CI, 1.02-1.39), and IBS (HR, 1.34; 95% CI, 1.19-1.50), but not H pylori infection (HR, 1.04; 95% CI, 0.96-1.13) or SIBO (HR, 0.71; 95% CI, 0.18-1.86). The researchers noted that further study is needed to determine potential common causal factors and examine the underlying mechanisms and clinical consequences of these associations.
Rosacea and the occurrence of cancer has also been investigated, but data is limited. In the ongoing Nurses’ Health Study II of more than 116,000 women who complete a biennial questionnaire on medical history and lifestyle practices, the more than 6,000 women with a diagnosis of rosacea were found to be 1.59 times more likely to have thyroid cancer and 1.5 times more likely to have basal cell carcinoma compared with those without rosacea.3,8
Because the potential link between rosacea and other cancers remains poorly investigated, Egeberg and colleagues9 recently examined that association between rosacea and selected cancers using health data from the Danish National Patient Registry. The researchers observed significant associations between rosacea and hepatic cancer (HR, 1.42; 95% CI, 1.06-1.90), nonmelanoma skin cancer (HR, 1.36; 95% CI, 1.26-1.47), and breast cancer (HR, 1.25; 95% CI, 1.15-1.36). Notably, the risk of lung cancer was significantly decreased among patients with rosacea (HR, 0.78; 95% CI, 0.69-0.89).
“These results are in contrast to the limited published data on cancers in rosacea, and further studies are warranted to elucidate the potential relationship between rosacea and various cancers,” concluded the researchers. “Potentially, factors such as skin color, alcohol intake, and tobacco use, which we were not able to control for in this report, may help explain some of these findings.”
Drs Harper and Baldwin, who are members of the NRS Medical Advisory Board, said they do not believe the recent surge of scientific studies showing a link between rosacea and various comorbidities has yet to impact how dermatologists diagnosis, manage, and treat rosacea.
“All of these studies are database studies that are able to show an association between the two conditions in question. These studies have my attention because of what they might teach us about the pathogenesis of rosacea and about inflammation in the skin and in the body in general,” said Dr Harper.
“If you have 16 million older people 40 to 60 years of age, it’s not surprising that a large number of them might have common medical conditions like GERD, IBD, Parkinson disease, and cardiovascular disease,” said Dr Baldwin. “We know that acne is associated with gastrointestinal problems. Psoriasis is associated with cardiovascular disease. It may be that inflammatory skin conditions are associated with inflammatory systemic conditions. If inflammation is the common connector, then the more inflamed you are, the more association there might be.” She suggested more attention to comorbidities may be appropriate for patients with more severe rosacea.
Article continues on page 3
{{pagebreak}}
Education Is Key
Dr Baldwin agreed that patient education about rosacea and its potential comorbidities is important. She said patients also need to be truthful about any symptoms they are experiencing when filling out patient health forms in the dermatology office and when seeing the dermatologist.
She also said that more education for dermatologists to recognize comorbidities associated with rosacea is warranted considering the amount of data being published. “I fear that these frequent articles [about rosacea and comorbidities] are numbing dermatologists to the real issue. There is a role for education in a rational and sensible way,” Dr Baldwin explained.
“The reason for education I think would be to tie together the various reported comorbidities and to focus in on a couple that make more medical sense and for which there is more medical data, such as gastrointestinal and cardiovascular disease,” she said.
To bring attention to the early warning signs of rosacea and encourage individuals who suspect they may have the disease to see a dermatologist for diagnosis and appropriate therapy, the NRS has designated April as Rosacea Awareness Month. Bulk quantities of educational materials are available to health care professionals for their patients through the NRS website.
The NRS offers Rosacea Review, a newsletter for patients; a “Rosacea Diary” to help patients identify and avoid lifestyle factors that may trigger flare-ups in their individual cases; and other booklets to help patients understand and manage their condition. For more information, visit the physicians section of the NRS website https://www.rosacea.org/physicians/.
References
1. Wu CY, Chang, YT, Juan CK. Risk of inflammatory bowel disease in patients with rosacea: Results from a nationwide cohort study in Taiwan [published online January 7, 2017]. J Am Acad Dermatol. doi:10.1016/j.jaad.2016.11.065
2. Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015;72(5):749-758.
3. Wolf JE Jr. Rosacea diagnosis and management. The Dermatologist. 2017;25(2):21-25.
4. What is rosacea. National Rosacea Society website. https://www.rosacea.org. Accessed March 28, 2017.
5. Wehausen B, Hill DE, Feldman SR. Most people with psoriasis or rosacea are not being treated: a large population study. Dermatol Online J. 2016;22(7). pii:13030/qt4nc3p4q2.
6. Rainer BM, Fischer AH, Luz Felipe da Silva D, Kang S, Chien AL. Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. J Am Acad Dermatol. 2015;73(4):604-608.
7. Egeberg A, Weinstock LB, Thyssen EP, Gislason GH, Thyssen JP. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017;176(1):100-106.
8. Li W-Q, Zhang M, Danby FW, Han J, Qureshi AA. Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer. 2015;113(3):520-523.
9. Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Rosacea and risk of cancer in Denmark. Cancer Epidemiol. 2017;47:76-80.
Rosacea is a common chronic inflammatory skin disorder of recurrent facial flushing of the central face that is estimated to affect 16 million Americans1,2; signs and symptoms typically first appear between 30 and 60 years of age. The disease consists of various combinations of primary and secondary signs and symptoms and varies from one patient to another, including flushing, erythema, telangiectasia, edema, papules, pustules, ocular lesions, and rhinophyma. It may include sensations of burning and stinging, as well as ocular symptoms of foreign-body sensation and dryness.3
The most common presentations of primary and secondary features have been designated as subtypes, and patients may have more than one subtype at a time. Subtype 1, erythematotelangiectatic rosacea, is characterized by flushing and persistent erythema on the central face without telangiectasia, edema, stinging, or roughness. Subtype 2, papulopustular rosacea, may consist of persistent erythema, papules, pustules, and burning/stinging. Subtype 3, phymatous rosacea, may include thickening skin, irregular nodularities, and enlargement, especially of the nose. Subtype 4, ocular rosacea, may comprise foreign-body sensation, burning/stinging, dryness, itching, photosensitivity, and blurred vision.3 Management options for rosacea include medical therapy, lifestyle modifications, and appropriate skin care.
Beyond its many potential physical effects, surveys by the National Rosacea Society (NRS) found rosacea can cause significant psychological, emotional, and occupational problems if left untreated.4 The pathogenesis of rosacea is unknown; however, new research has linked the disease to increased risk of various comorbidities.
This article looks at the prevalence of rosacea and highlights recent studies on the association between rosacea and other diseases and if the results are impacting how dermatologists diagnose, manage, and treat this cutaneous disorder.
Disease Prevalence
Only a small fraction of the 16 million individuals living with rosacea are seeking treatment, according to data from a large population study that showed an estimated 82% of individuals are currently untreated.5
“It is difficult to understand why so many people don’t seek treatment. They may think that they have adult acne and try to self-treat. They may be embarrassed to make an appointment and to talk to someone about their skin,” said Julie C. Harper, MD, who is in private practice at the Dermatology and Skin Care Center of Birmingham and clinical associate professor of dermatology at the University of Alabama at Birmingham, in an interview with The Dermatologist. “The lay population have long associated rosacea with alcohol consumption and they may feel shamed by that association even if they are nondrinkers. All of these things boil down to a lack of understanding and awareness of what rosacea is.”
Hilary Baldwin, MD, medical director of the Acne Treatment and Research Center (Morristown, NJ) and clinical associate professor of dermatology at Rutgers University, who was also interviewed, agreed there is a lack of patient awareness. “I have seen people come into my office with relatively bad rosacea who are there to discuss another condition,” she said, noting that signs and symptoms of the disease may not bother patients, and they may not be aware they have a disease or that treatments are available.
Article continues on page 2
{{pagebreak}}
Rosacea and Comorbidities
Recent medical research has suggested that rosacea may also be associated with systemic diseases, neurologic diseases, certain types of cancer and more. A 2015 case-control study conducted by Rainer and colleagues6 at Johns Hopkins University of 130 individuals with rosacea found a significant association between rosacea and allergies, gastroesophageal reflux disease (GERD), other gastrointestinal (GI) diseases, hypertension, metabolic and urogenital diseases, and female hormone imbalance.
Additionally, moderate to severe rosacea was associated with hyperlipidemia, hypertension, metabolic diseases, cardiovascular disease and GERD.
“Physicians should be aware of these associations to provide comprehensive care to patients with rosacea, especially to those presenting with more severe disease,” the researchers concluded.
Recent findings of large-scale studies of health data in Taiwan1 and from the Danish National Patient Registry7 have demonstrated potential associations between rosacea and inflammatory bowel disease (IBD) and GI disorders.
Wu and colleagues1 investigated the link between rosacea and IBD, including Crohn disease and ulcerative colitis, in a nationwide cohort study of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 who were identified in the Taiwanese National Health Insurance Research Database. The researchers also examined the effects of antibiotics.
The 15-year cumulative incidences of IBD showed a small increased risk in patients with rosacea (0.036; 95% CI, 0.00-1.5) compared with patients without the disease (0.019; 95% CI, 0.00-0.83). Rosacea (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.04-3.63) and male gender (aHR, 3.52; 95% CI, 2.03-6.11) were independently associated with IBD, after adjustment for major comorbidities. These results were consistent across different subgroups of patients on multivariate subgroup analyses.
A sensitivity analysis that examined the association between antibiotic treatment and subsequent IBD in patients with rosacea demonstrated that long-term frequent antibiotic users had lower incidence of IBD, but without statistical significance. The researchers noted that the link between long-term antibiotic use and the development of IBD warrants further investigation.
A separate study7 examined the link between rosacea and certain GI disorders, with a focus on celiac disease, Crohn disease, ulcerative colitis, Helicobactor pylori infection, small intestinal bacterial overgrowth (SIBO), and irritable bowel syndrome (IBS). The researchers selected these conditions due to their mechanistic and pathogenic overlap with rosacea.
As in their previous comorbidity studies, Egeberg and colleagues tracked more than 4.3 million individuals in the Danish National Patient Registry for 5 years, including 49,475 who were diagnosed with rosacea. The researchers found a higher prevalence of these 6 GI disorders among patients with rosacea compared with the control group. Adjusted HRs showed significant associations between rosacea and celiac disease (HR, 1.46; 95% CI, 1.11-1.93), Crohn disease (HR, 1.45; 95% CI, 1.19-1.77), ulcerative colitis (HR, 1.19; 95% CI, 1.02-1.39), and IBS (HR, 1.34; 95% CI, 1.19-1.50), but not H pylori infection (HR, 1.04; 95% CI, 0.96-1.13) or SIBO (HR, 0.71; 95% CI, 0.18-1.86). The researchers noted that further study is needed to determine potential common causal factors and examine the underlying mechanisms and clinical consequences of these associations.
Rosacea and the occurrence of cancer has also been investigated, but data is limited. In the ongoing Nurses’ Health Study II of more than 116,000 women who complete a biennial questionnaire on medical history and lifestyle practices, the more than 6,000 women with a diagnosis of rosacea were found to be 1.59 times more likely to have thyroid cancer and 1.5 times more likely to have basal cell carcinoma compared with those without rosacea.3,8
Because the potential link between rosacea and other cancers remains poorly investigated, Egeberg and colleagues9 recently examined that association between rosacea and selected cancers using health data from the Danish National Patient Registry. The researchers observed significant associations between rosacea and hepatic cancer (HR, 1.42; 95% CI, 1.06-1.90), nonmelanoma skin cancer (HR, 1.36; 95% CI, 1.26-1.47), and breast cancer (HR, 1.25; 95% CI, 1.15-1.36). Notably, the risk of lung cancer was significantly decreased among patients with rosacea (HR, 0.78; 95% CI, 0.69-0.89).
“These results are in contrast to the limited published data on cancers in rosacea, and further studies are warranted to elucidate the potential relationship between rosacea and various cancers,” concluded the researchers. “Potentially, factors such as skin color, alcohol intake, and tobacco use, which we were not able to control for in this report, may help explain some of these findings.”
Drs Harper and Baldwin, who are members of the NRS Medical Advisory Board, said they do not believe the recent surge of scientific studies showing a link between rosacea and various comorbidities has yet to impact how dermatologists diagnosis, manage, and treat rosacea.
“All of these studies are database studies that are able to show an association between the two conditions in question. These studies have my attention because of what they might teach us about the pathogenesis of rosacea and about inflammation in the skin and in the body in general,” said Dr Harper.
“If you have 16 million older people 40 to 60 years of age, it’s not surprising that a large number of them might have common medical conditions like GERD, IBD, Parkinson disease, and cardiovascular disease,” said Dr Baldwin. “We know that acne is associated with gastrointestinal problems. Psoriasis is associated with cardiovascular disease. It may be that inflammatory skin conditions are associated with inflammatory systemic conditions. If inflammation is the common connector, then the more inflamed you are, the more association there might be.” She suggested more attention to comorbidities may be appropriate for patients with more severe rosacea.
Article continues on page 3
{{pagebreak}}
Education Is Key
Dr Baldwin agreed that patient education about rosacea and its potential comorbidities is important. She said patients also need to be truthful about any symptoms they are experiencing when filling out patient health forms in the dermatology office and when seeing the dermatologist.
She also said that more education for dermatologists to recognize comorbidities associated with rosacea is warranted considering the amount of data being published. “I fear that these frequent articles [about rosacea and comorbidities] are numbing dermatologists to the real issue. There is a role for education in a rational and sensible way,” Dr Baldwin explained.
“The reason for education I think would be to tie together the various reported comorbidities and to focus in on a couple that make more medical sense and for which there is more medical data, such as gastrointestinal and cardiovascular disease,” she said.
To bring attention to the early warning signs of rosacea and encourage individuals who suspect they may have the disease to see a dermatologist for diagnosis and appropriate therapy, the NRS has designated April as Rosacea Awareness Month. Bulk quantities of educational materials are available to health care professionals for their patients through the NRS website.
The NRS offers Rosacea Review, a newsletter for patients; a “Rosacea Diary” to help patients identify and avoid lifestyle factors that may trigger flare-ups in their individual cases; and other booklets to help patients understand and manage their condition. For more information, visit the physicians section of the NRS website https://www.rosacea.org/physicians/.
References
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2. Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015;72(5):749-758.
3. Wolf JE Jr. Rosacea diagnosis and management. The Dermatologist. 2017;25(2):21-25.
4. What is rosacea. National Rosacea Society website. https://www.rosacea.org. Accessed March 28, 2017.
5. Wehausen B, Hill DE, Feldman SR. Most people with psoriasis or rosacea are not being treated: a large population study. Dermatol Online J. 2016;22(7). pii:13030/qt4nc3p4q2.
6. Rainer BM, Fischer AH, Luz Felipe da Silva D, Kang S, Chien AL. Rosacea is associated with chronic systemic diseases in a skin severity-dependent manner: results of a case-control study. J Am Acad Dermatol. 2015;73(4):604-608.
7. Egeberg A, Weinstock LB, Thyssen EP, Gislason GH, Thyssen JP. Rosacea and gastrointestinal disorders: a population-based cohort study. Br J Dermatol. 2017;176(1):100-106.
8. Li W-Q, Zhang M, Danby FW, Han J, Qureshi AA. Personal history of rosacea and risk of incident cancer among women in the US. Br J Cancer. 2015;113(3):520-523.
9. Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Rosacea and risk of cancer in Denmark. Cancer Epidemiol. 2017;47:76-80.
