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Original Paper

Free Access

Patients with Rosacea Have Increased Risk of Depression and Anxiety Disorders: A Danish Nationwide Cohort Study

Egeberg A.a, b · Hansen P.R.b · Gislason G.H.b · Thyssen J.P.a

Author affiliations

aNational Allergy Research Centre, Department of Dermato-Allergology, and bDepartment of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

Corresponding Author

Alexander Egeberg

Department of Dermato-Allergology, Herlev and Gentofte Hospital

University of Copenhagen, Kildegårdsvej 28

DK-2900 Hellerup (Denmark)

E-Mail alexander.egeberg@gmail.com

Related Articles for ""

Dermatology 2016;232:208-213

Abstract

Background: Rosacea is a chronic skin condition that affects self-esteem and quality of life. However, data on depression and anxiety in patients with rosacea are scarce. Objective: The aim of this study was to investigate the relationship between rosacea and new-onset depression and anxiety disorders. Methods: Data on all Danish citizens aged ≥18 years between January 1, 1997, and December 31, 2011, were linked at individual level in nationwide registers. Incidence rates per 1,000 person-years were calculated, and crude and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were estimated by Poisson regression models. Results: The study comprised a total of 4,632,341 individuals, including 30,725 and 24,712 patients with mild and moderate-to-severe rosacea, respectively. Mild and moderate-to-severe rosacea increased the risk of both depression [IRR 1.89 (95% CI 1.82-1.96) and IRR 2.04 (95% CI 1.96-2.12)] and anxiety disorders [IRR 1.80 (95% CI 1.75-1.86) and IRR 1.98 (95% CI 1.91-2.05)]. Conclusions: Rosacea was associated with a disease severity-dependent, increased risk of depression and anxiety disorders. The findings may call for increased awareness of psychiatric morbidity in patients with rosacea.

© 2016 S. Karger AG, Basel


Introduction

Rosacea is a common chronic inflammatory skin condition characterized primarily by transient or persistent centrofacial erythema, pustules, and telangiectasia [1,2,3,4]. The National Rosacea Society Expert Committee recognizes four subtypes of rosacea: (i) erythematotelangiectatic, (ii) inflammatory papulopustular, (iii) phymatous, and (iv) ocular. Erythematotelangiectatic and papulopustular rosacea are predominantly treated with topical or systemic anti-inflammatory antibiotics, whereas low-dose oral vitamin A can be used for prolonged treatment, and dye laser therapy for cosmetically disfiguring telangiectasia. Phymatous rosacea (rhinophyma) is primarily diagnosed in male patients and is clinically dominated by hyperplasia of the nasal sebaceous glands. Antibiotics are here effective, but in chronic and severe cases, cosmetic CO2 laser evaporation is used.

Although the etiopathogenesis of rosacea is complex and not fully understood, neurovascular dysregulation and neurogenic inflammation are central [4]. Environmental triggers, including Demodex, temperature change, ultraviolet irradiation, alcohol consumption, and spicy foods, can stimulate the release of various cytokines, in particular antimicrobial peptides, e.g. cathelicidin. The adaptive immune system can also be activated resulting in a predominance of cutaneous T helper (Th)1 and Th17 cell infiltrates [5]. Moreover, expression of certain matrix metalloproteinases (MMPs) and the number of pain-transmitting myelinated nerve fibers are increased in rosacea [4,6].

Due to facial cosmetically unpleasant changes, rosacea can clearly have a profound negative effect on a person's self-esteem [6]. Rosacea has also been associated with a decreased quality of life, and the prevalence of depression and anxiety is higher in patients with rosacea when compared with healthy controls [7,8]. Interestingly, although the co-occurrence of depression may primarily be attributed to the cosmetic changes in patients with rosacea, both conditions share a strong inflammatory component [9,10,11,12]. Also, it has previously been suggested that dermatologists tend to underestimate the occurrence of psychiatric disorders in many skin conditions [13]. We therefore investigated the association between rosacea, depression and anxiety disorders in a nationwide cohort of the Danish population.

Materials and Methods

For further details, see online supplementary materials (see www.karger.com/doi/10.1159/000444082 for all online suppl. material) [6,14,15,16,17,18,19,20,21] and figure 1.

Fig. 1

Flowchart of the study design.

http://www.karger.com/WebMaterial/ShowPic/497014

Results

From the initial cohort of individuals aged 18 years or older from January 1, 1997, to December 31, 2011 (n = 5,536,422), we excluded 5,705 individuals with prevalent rosacea, 858,342 individuals using antidepressants or anxiolytics prior to the study start, and 2,130 individuals with both prevalent rosacea and use of antidepressant or anxiolytics prior to study start. Also, we excluded 37,904 individuals with incomplete information on migration. The final cohort comprised a total of 4,632,341 individuals, and during the maximum follow-up of 15 years, we identified a total of 55,437 patients with incident rosacea, including 30,725 with mild and 24,712 with moderate-to-severe rosacea. The mean ages were 37.7, 41.3, and 38.1 years among the reference population, and subjects with mild and moderate-to-severe rosacea, respectively (table 1).

Table 1

Baseline characteristics of the study population

http://www.karger.com/WebMaterial/ShowPic/497017

Risk of Depression in Patients with Mild and Moderate-to-Severe Rosacea

Incidence rates of depression per 1,000 person-years were 15.20, 32.78, and 34.26 for the reference population, and subjects with mild and moderate-to-severe rosacea, respectively (table 2). Fully adjusted incidence rate ratios (IRRs) for depression were 1.89 [95% confidence interval (CI) 1.82-1.96] and 2.04 (95% CI 1.96-2.12) for mild and moderate-to-severe rosacea, respectively (table 3). Stratified by sex, the risk of depression was significantly increased in women with mild (IRR 1.89, 95% CI 1.81-1.97) and moderate-to-severe (IRR 2.10, 95% CI 2.01-2.20) rosacea. In men, the risk of depression was similar among individuals with mild (IRR 1.86, 95% CI 1.74-1.98) and moderate-to-severe (IRR 1.84, 95% CI 1.71-1.98) rosacea. Stratified by age, the crude IRRs of depression were 2.17 (95% CI 2.10-2.25) and 2.31 (95% CI 2.22-2.40) for mild and moderate-to-severe rosacea, respectively, in younger (<40 years of age) individuals, versus 1.71 (95% CI 1.43-2.04) and 1.97 (95% CI 1.43-2.72) in older (≥40 years of age) individuals, respectively. The results were similar in fully adjusted estimates and in both genders (online suppl. appendix). After additional stratification by socioeconomic status, the fully adjusted IRRs in rosacea patients with low socioeconomic status (index ≤2) were 1.88 (95% CI 1.80-1.98) and 2.15 (95% CI 2.03-2.27) for mild and moderate-to-severe rosacea, respectively, and in patients with higher (index >2) socioeconomic status, the risk estimates were 1.88 (95% CI 1.78-1.97) and 1.91 (95% CI 1.80-2.02). A trend test for the association between socioeconomic status and depression in patients with moderate-to-severe rosacea confirmed our primary findings (p for trend <0.001).

Table 2

Incidence rates of depression and anxiety disorders per 1,000 person-years in the reference population, and patients with mild and moderate-to-severe rosacea, respectively

http://www.karger.com/WebMaterial/ShowPic/497016

Table 3

IRRs of depression and anxiety disorders in patients with mild and moderate-to-severe rosacea

http://www.karger.com/WebMaterial/ShowPic/497015

Risk of Anxiety Disorders in Patients with Mild and Moderate-to-Severe Rosacea

The incidence rates per 1,000 person-years of anxiety disorders were 22.15, 48.77, and 49.05 for the reference population, and subjects with mild and moderate-to-severe rosacea, respectively. Fully adjusted IRRs for anxiety disorders were 1.80 (95% CI 1.75-1.86) and 1.98 (95% CI 1.91-2.05) for mild and moderate-to-severe rosacea, respectively. In women, the risk of anxiety disorders was significantly increased in mild (IRR 1.81, 95% CI 1.75-1.88) and moderate-to-severe rosacea (IRR 2.01, 95% CI 1.93-2.09). Similarly, the risk of anxiety disorders was significantly increased in men with mild (IRR 1.74, 95% CI 1.65-1.83) and moderate-to-severe rosacea (IRR 1.87, 95% CI 1.75-1.98). Age stratification revealed IRRs of 2.23 (95% CI 2.16-2.30) and 2.31 (95% CI 2.23-2.39) in younger individuals with mild and moderate-to-severe rosacea, respectively, versus 1.61 (95% CI 1.41-1.84) and 1.59 (95% CI 1.20-2.11) in older individuals, respectively. Age-stratified results remained consistent in fully adjusted analyses, and in estimates of women as well as men (data not shown). In rosacea patients with low socioeconomic status, IRRs were 1.83 (95% CI 1.75-1.91) for mild and 2.02 (95% CI 1.92-2.13) for moderate-to-severe rosacea, and in patients with high socioeconomic status, IRRs were 1.77 (95% CI 1.69-1.84) and 1.94 (95% CI 1.85-2.03). A trend test confirmed these findings (p for trend <0.001) in mild and moderate-to-severe rosacea.

In subanalyses of patients with rhinophyma and patients treated with CO2 and dye laser, the results were essentially similar to the primary analyses (online suppl. appendix), except for patients treated with CO2 laser, where the risk of depression was not significant (IRR 1.76, 95% CI 0.88-3.52, p = 0.110). In sensitivity analyses where the outcome was a hospital diagnosis of depression or anxiety disorders, the results remained similar to our primary analyses (data not shown).

Discussion

In this nationwide cohort of the Danish population with a maximum follow-up of 15 years, we found a disease severity-dependent, increased risk of new-onset anxiety disorders and depression in patients with rosacea. The results remained consistent after adjustment for comorbidities and in sensitivity analyses. The highest risk of anxiety disorders and depression occurred in younger patients. Also, a low socioeconomic status appeared to increase the risk of depression in those with moderate-to-severe rosacea. While limited studies have reported a negative effect of rosacea on quality of life, and an increased co-occurrence of depression in patients with rosacea, the independent impact of rosacea on the risk of new-onset depression has not been shown previously to our knowledge.

Depression and anxiety disorders appear to be common comorbidities in a range of dermatological conditions, including psoriasis and hidradenitis suppurativa [19,22]. Analyses from a health care survey of patients with rosacea from the United States between 1995 and 2002 reported an odds ratio of 4.81 for co-occuring depression [8]. However, these calculations were based on the number of patient visits to dermatological practices, and the exact number of patients was not reported. Also, a German questionnaire-based study of patients with rosacea (total n = 168) found rosacea to be associated with considerable anxiety disorders and depression scores [23]. Indeed, in a recent review article of the literature, the authors concluded that depression and anxiety disorders occurred more frequently in patients with rosacea, and that quality of life tended to be decreased in these patients [7]. In addition, a significant improvement in quality of life following use of decorative cosmetics in patients with rosacea and other skin diseases has been reported, which could suggest that the centrofacial localization of rosacea is a major cause of the observed association between rosacea and depression [24]. It is, however, intriguing that rosacea and depression may share certain overlaps in their inflammatory pathways [5,9,10,11,12]. In addition, MMPs contribute to the pathophysiology of rosacea and studies have found increased serum MMP levels in patients with depression [25,26]. Therefore, the mechanisms underlying the association between rosacea, depression and anxiety disorders, and the relationship between these diseases and their respective treatment, clearly require further study. Although the observed 76% increased risk of depression in patients treated with CO2 laser was not statistically significant, this may have been a power issue owing to the small cohort studied.

Certain limitations and strengths apply to the present study. The high accuracy of the Danish registries allows for large-scale nationwide analyses, in which selection bias and recall bias are minimized. Indeed, previous studies on the association between rosacea and depression and anxiety disorders have all been small studies of selected patients, and our study, therefore, expands the existing evidence considerably. In addition, the available information and continuous update of comorbidities during follow-up allow for adjustment of potential risk factors for depression, which could change over time. We used prescriptions of topical metronidazole, antidepressants, and anxiolytics as measures of rosacea, depression, and anxiety disorders, respectively. While it is possible that some misclassification could have occurred, e.g. due to uncommon treatment with certain forms of antidepressants for rosacea-associated neuralgia, we do not suspect this to have substantially affected the study outcome [27]. Importantly, although patients with anxiety disorders are frequently treated with antidepressants [28], sensitivity analyses using specific diagnoses of depression yielded results that were generally in accordance with those of our primary analyses. In addition, tetracycline is also routinely used in the treatment of acne vulgaris, but since topical metronidazole therapy is not used for this condition, any misclassification related to tetracycline use in this specific cohort is likely negligible. However, such hypothetical misclassification would arguably bias our results towards the null. Importantly, minocycline is not marketed in Denmark. Finally, the Danish population is predominantly of Northern European decent, and thus the generalizability of the results to other ethnicities should be done with caution.

In conclusion, we found a disease severity-dependent, increased risk of depression and anxiety disorders in Danish patients with rosacea. The findings highlight the importance of a holistic approach in the evaluation and treatment of patients with dermatological disorders, and further studies are warranted to determine the underlying mechanisms and effects of pharmacological treatment of rosacea on this association.

Statement of Ethics

Review of an ethics committee is not required for register studies in Denmark.

Disclosure Statement

Dr. Egeberg has received a grant from Pfizer, Dr. Hansen is supported by an unrestricted grant from the LEO Foundation, Dr. Gislason is supported by an unrestricted research scholarship from the Novo Nordisk Foundation, and Dr. Thyssen is supported by an unrestricted grant from the Lundbeck Foundation.

This research was performed independently through the authors' academic university affiliations. Pfizer, the LEO foundation, the Novo Nordisk Foundation, and the Lundbeck Foundation had no involvement in the study design, the collection, analysis, and interpretation of data, the writing of the report, or in the decision to submit the paper for publication, respectively.


References

  1. Lomholt G: Prevalence of skin diseases in a population; a census study from the Faroe Islands. Dan Med Bull 1964;11:1-7.
    External Resources
  2. Berg M, Liden S: An epidemiological study of rosacea. Acta Derm Venereol 1989;69:419-423.
  3. Tan J, Blume-Peytavi U, Ortonne JP, Wilhelm K, Marticou L, Baltas E, Rivier M, Petit L, Martel P: An observational cross-sectional survey of rosacea: clinical associations and progression between subtypes. Br J Dermatol 2013;169:555-562.
  4. Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, Rivier M, Carlavan I, Rossio P, Metze D, Buddenkotte J, Cevikbas F, Voegel JJ, Steinhoff M: Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 2011;15:53-62.
  5. Buhl T, Sulk M, Nowak P, Buddenkotte J, McDonald I, Aubert J, Carlavan I, Deret S, Reiniche P, Rivier M, Voegel JJ, Steinhoff M: Molecular and morphological characterization of inflammatory infiltrate in rosacea reveals activation of Th1/Th17 pathways. J Invest Dermatol 2015;135:2198-2208.
  6. Two AM, Wu W, Gallo RL, Hata TR: Rosacea. Part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol 2015;72:749-758.
  7. Moustafa F, Lewallen RS, Feldman SR: The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol 2014;71:973-980.
  8. Gupta MA, Gupta AK, Chen SJ, Johnson AM: Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey - Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002. Br J Dermatol 2005;153:1176-1181.
  9. Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O, Sanisoglu SY, Yesilova Z, Ozmenler N, Ozsahin A, Sengul A: Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol 2007;2007:76396.
  10. Maes M: Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:664-675.
  11. Miller AH: Depression and immunity: a role for T cells? Brain Behav Immun 2010;24:1-8.
  12. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL: A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-457.
  13. Sampogna F, Picardi A, Melchi CF, Pasquini P, Abeni D: The impact of skin diseases on patients: comparing dermatologists' opinions with research data collected on their patients. Br J Dermatol 2003;148:989-995.
  14. Schmidt M, Pedersen L, Sorensen HT: The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 2014;29:541-549.
  15. Baadsgaard M, Quitzau J: Danish registers on personal income and transfer payments. Scand J Public Health 2011;39:103-105.
  16. Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 1999;46:263-268.
  17. Gaist D, Sorensen HT, Hallas J: The Danish prescription registries. Dan Med Bull 1997;44:445-448.
    External Resources
  18. Egeberg A, Mallbris L, Gislason GH, Skov L, Hansen PR: Risk of multiple sclerosis in patients with psoriasis: a Danish nationwide cohort study. J Invest Dermatol 2016;136:93-98.
  19. Jensen P, Ahlehoff O, Egeberg A, Gislason G, Hansen PR, Skov L: Psoriasis and new-onset depression: a Danish nationwide cohort study. Acta Derm Venereol 2016;96:39-42.
  20. Rist PM, Schurks M, Buring JE, Kurth T: Migraine, headache, and the risk of depression: prospective cohort study. 2013;33:1017-1025.
  21. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, STROBE Initiative: The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Epidemiology 2007;18:800-804.
  22. Vazquez BG, Alikhan A, Weaver AL, Wetter DA, Davis MD: Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota. J Invest Dermatol 2013;133:97-103.
  23. Bohm D, Schwanitz P, Stock Gissendanner S, Schmid-Ott G, Schulz W: Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med 2014;19:586-591.
  24. Boehncke WH, Ochsendorf F, Paeslack I, Kaufmann R, Zollner TM: Decorative cosmetics improve the quality of life in patients with disfiguring skin diseases. Eur J Dermatol 2002;12:577-580.
    External Resources
  25. Garvin P, Nilsson L, Carstensen J, Jonasson L, Kristenson M: Plasma levels of matrix metalloproteinase-9 are independently associated with psychosocial factors in a middle-aged normal population. Psychosom Med 2009;71:292-300.
  26. Rybakowski JK, Remlinger-Molenda A, Czech-Kucharska A, Wojcicka M, Michalak M, Losy J: Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients during bipolar depression. J Affect Disord 2013;146:286-289.
  27. Scharschmidt TC, Yost JM, Truong SV, Steinhoff M, Wang KC, Berger TG: Neurogenic rosacea: a distinct clinical subtype requiring a modified approach to treatment. Arch Dermatol 2011;147:123-126.
  28. Martin-Merino E, Ruigomez A, Wallander MA, Johansson S, Garcia-Rodriguez LA: Prevalence, incidence, morbidity and treatment patterns in a cohort of patients diagnosed with anxiety in UK primary care. Fam Pract 2010;27:9-16.

Author Contacts

Alexander Egeberg

Department of Dermato-Allergology, Herlev and Gentofte Hospital

University of Copenhagen, Kildegårdsvej 28

DK-2900 Hellerup (Denmark)

E-Mail alexander.egeberg@gmail.com


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 19, 2015
Accepted: January 15, 2016
Published online: March 09, 2016
Issue release date: April 2016

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 3

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: https://www.karger.com/DRM


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References

  1. Lomholt G: Prevalence of skin diseases in a population; a census study from the Faroe Islands. Dan Med Bull 1964;11:1-7.
    External Resources
  2. Berg M, Liden S: An epidemiological study of rosacea. Acta Derm Venereol 1989;69:419-423.
  3. Tan J, Blume-Peytavi U, Ortonne JP, Wilhelm K, Marticou L, Baltas E, Rivier M, Petit L, Martel P: An observational cross-sectional survey of rosacea: clinical associations and progression between subtypes. Br J Dermatol 2013;169:555-562.
  4. Schwab VD, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C, Rivier M, Carlavan I, Rossio P, Metze D, Buddenkotte J, Cevikbas F, Voegel JJ, Steinhoff M: Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc 2011;15:53-62.
  5. Buhl T, Sulk M, Nowak P, Buddenkotte J, McDonald I, Aubert J, Carlavan I, Deret S, Reiniche P, Rivier M, Voegel JJ, Steinhoff M: Molecular and morphological characterization of inflammatory infiltrate in rosacea reveals activation of Th1/Th17 pathways. J Invest Dermatol 2015;135:2198-2208.
  6. Two AM, Wu W, Gallo RL, Hata TR: Rosacea. Part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol 2015;72:749-758.
  7. Moustafa F, Lewallen RS, Feldman SR: The psychological impact of rosacea and the influence of current management options. J Am Acad Dermatol 2014;71:973-980.
  8. Gupta MA, Gupta AK, Chen SJ, Johnson AM: Comorbidity of rosacea and depression: an analysis of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Care Survey - Outpatient Department data collected by the U.S. National Center for Health Statistics from 1995 to 2002. Br J Dermatol 2005;153:1176-1181.
  9. Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O, Sanisoglu SY, Yesilova Z, Ozmenler N, Ozsahin A, Sengul A: Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol 2007;2007:76396.
  10. Maes M: Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:664-675.
  11. Miller AH: Depression and immunity: a role for T cells? Brain Behav Immun 2010;24:1-8.
  12. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL: A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-457.
  13. Sampogna F, Picardi A, Melchi CF, Pasquini P, Abeni D: The impact of skin diseases on patients: comparing dermatologists' opinions with research data collected on their patients. Br J Dermatol 2003;148:989-995.
  14. Schmidt M, Pedersen L, Sorensen HT: The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 2014;29:541-549.
  15. Baadsgaard M, Quitzau J: Danish registers on personal income and transfer payments. Scand J Public Health 2011;39:103-105.
  16. Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 1999;46:263-268.
  17. Gaist D, Sorensen HT, Hallas J: The Danish prescription registries. Dan Med Bull 1997;44:445-448.
    External Resources
  18. Egeberg A, Mallbris L, Gislason GH, Skov L, Hansen PR: Risk of multiple sclerosis in patients with psoriasis: a Danish nationwide cohort study. J Invest Dermatol 2016;136:93-98.
  19. Jensen P, Ahlehoff O, Egeberg A, Gislason G, Hansen PR, Skov L: Psoriasis and new-onset depression: a Danish nationwide cohort study. Acta Derm Venereol 2016;96:39-42.
  20. Rist PM, Schurks M, Buring JE, Kurth T: Migraine, headache, and the risk of depression: prospective cohort study. 2013;33:1017-1025.
  21. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, STROBE Initiative: The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Epidemiology 2007;18:800-804.
  22. Vazquez BG, Alikhan A, Weaver AL, Wetter DA, Davis MD: Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota. J Invest Dermatol 2013;133:97-103.
  23. Bohm D, Schwanitz P, Stock Gissendanner S, Schmid-Ott G, Schulz W: Symptom severity and psychological sequelae in rosacea: results of a survey. Psychol Health Med 2014;19:586-591.
  24. Boehncke WH, Ochsendorf F, Paeslack I, Kaufmann R, Zollner TM: Decorative cosmetics improve the quality of life in patients with disfiguring skin diseases. Eur J Dermatol 2002;12:577-580.
    External Resources
  25. Garvin P, Nilsson L, Carstensen J, Jonasson L, Kristenson M: Plasma levels of matrix metalloproteinase-9 are independently associated with psychosocial factors in a middle-aged normal population. Psychosom Med 2009;71:292-300.
  26. Rybakowski JK, Remlinger-Molenda A, Czech-Kucharska A, Wojcicka M, Michalak M, Losy J: Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients during bipolar depression. J Affect Disord 2013;146:286-289.
  27. Scharschmidt TC, Yost JM, Truong SV, Steinhoff M, Wang KC, Berger TG: Neurogenic rosacea: a distinct clinical subtype requiring a modified approach to treatment. Arch Dermatol 2011;147:123-126.
  28. Martin-Merino E, Ruigomez A, Wallander MA, Johansson S, Garcia-Rodriguez LA: Prevalence, incidence, morbidity and treatment patterns in a cohort of patients diagnosed with anxiety in UK primary care. Fam Pract 2010;27:9-16.
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