1 INTRODUCTION

Psoriasis is a chronic, hyperproliferative, inflammatory, and autoimmune condition of the skin. It is a multifactorial disease associated with a genetic predisposition, health status, and numerous environmental factors.1, 2 Smoking, alcohol, drugs, diet, infections, and stress are all known to aggravate psoriasis.3, 4 Thus, seasonal influence on psoriasis is likely to be orchestrated by a range of other factors as well as controlling disease activity at any time.

The overall prevalence of psoriasis is estimated to be 3%, but major geographical and ethnic variations have been reported worldwide.2 Psoriasis is more frequent on the European continent with a prevalence of around 2–3%. Race along with geography seems to be a decisive influencing factor. In the United States, psoriasis has been found in 6.5/1000 of White in contrast to 0.6/1000 in African Americans.2, 3

In research settings, the Northern and Central European climate is generally accepted as an index climate for observing the seasonal influence on skin diseases. Northern and Central Europe is due to the high prevalence of psoriasis and dissimilar seasonal weather, for example, cold winters and warm summers, suited for the study of the seasonal influence on psoriasis.

It is believed that exposure to sunlight has a positive influence on psoriasis particularly in skin type III and IV (rarely and never tanned).5 Ultraviolet B (UVB) phototherapy and climatotherapy, representing aggressive use of sunlight, are well adapted in the treatment of psoriasis. The positive effect of light therapy has probably shaped the idea of seasonal variation and psoriasis with automatic improvement in summer, defined as the sunny period. Contrarily, it is a general assumption that lack of sunlight and lower temperatures influence psoriasis negatively. However, the daily sun exposure and temperature represent two different physiological vectors. For instance, heat may dilate the cutaneous vasculature and create swelling and itch on a psoriatic plaque.

Several variables can affect psoriasis, and to study seasonal variation independently is unrealistic.

Patients with a chronic condition like psoriasis will experience a range of psychosocial problems such as worry, elevated levels of anxiety, and depression.6 Psychological distress is a common part of the illness, which negatively affects both disease severity and quality of life (DLQI).7, 8 The fact that stress is a foremost trigger on the onset and exacerbation of psoriasis has been emphasized for many years.4, 5, 9, 10

In addition to this, psychological well-being can also be changed by season with depression being more frequent in the dark winter season.11, 12 Seasonal affective disorder (SAD) is a systematic seasonal pattern of mood disorders. It is unsure whether SAD is a categorical diagnosis or an extreme form of a dimensional seasonality trait. Yet, even people with subsyndromal SAD still experience distress and functional impairment during the winter.13 The prevalence of SAD correlates with latitude but not with other environmental factors such as cloud, sunshine hours, snowfall, etc.13

With the high prevalence of seasonal mood problems and the limited daylight during winter in Northern Europe, SAD or subsyndromal SAD needs to be noted when analyzing the seasonal variation of psoriasis.14-16

Lastly, the use of modern therapies makes it challenging to isolate the effects of seasonal variation. Since the introduction of topical steroids and methotrexate around 1958, these efficient treatments have been widely used and significantly modified the spontaneous disease. Also, retinoids, ciclosporin, PUVA (psoralen and ultraviolet A), and biological treatments have changed the course and status of moderate to severe psoriasis. Today many patients have achieved clear state psoriasis the whole year.

To review the medical evidence of seasonal influence on psoriasis, we aim to systematically evaluate Northern and Central European studies grouped before and after the introduction of topical steroids and later systemic treatments.

2 MATERIAL AND METHODS

References for this review were identified using the following index words in the PUBMED database: “psoriasis AND seasonal variation” and “psoriasis AND seasonality.” Supplementary searches were made in EMBASE, BIOSIS, and Cochrane to ensure enrolment of all relevant studies.

We included only studies from Northern and Central Europe to ensure that surveys used to illustrate the seasonal variation on psoriasis were comparable.

We independently assessed all publications. In a primary, screening titles and abstracts were inspected for further enrolment. In the secondary screening, full-text versions of relevant articles were evaluated by study design, relevance, and country of origin. The reference lists of all enrolled articles were reviewed for additional articles of interest. With the purpose to find relevant material of older origin, a search for references from chosen articles, textbooks, and local libraries was performed. In this study, it was of major interest to include literature from before the introduction of topical corticoids and other modern therapies, so the effects from seasonal variation are less modified.

2.1 Measuring seasonal variation according to an evidence-based methodology

Studies on psoriasis and seasonality follow very different protocols, and it is not possible to perform a statistical meta-analysis. Therefore, the literature measuring seasonal variation was assessed using the Cochrane principles of ranking studies on therapies, disease prevention, and quality improvement operate with seven levels17 (see Table 1).

TABLE 1. Cochrane principles of ranking studies Study ranking I A randomized controlled trial (RCT) that demonstrates a statistically significant difference in at least one important outcome (not possible to apply in this review). II An RCT that does not meet level I criteria (not possible to apply in this review). III A nonrandomized trial with contemporaneous controls selected by some systematic method (i.e., not selected by a perceived suitability for one of the treatment options for individual patients) or subgroup analysis of an RCT (not possible to apply in this review). IV Case series (of at least 10 patients) with historical controls or controls drawn from other studies. V Case series (at least 10 patients without controls) VI Case report (fewer than 10 patients) VII Expert opinion Method used to specify design a Cases measured with recognized standardized methods (quantitative) b Cases with measurable objective endpoints (quantitative). c Cases with a personal interview by the investigator (qualitative) d Cases based on questionnaires (qualitative)

Surveys based on expert opinions were found of little value to this review and have been excluded. The RCT design does not apply to any prospective assessment of seasonal influence on psoriasis since a nonseason randomized controlled group cannot be established. Thus, studying psoriasis and seasonal variation, Cochrane ranking level IV would be the highest level of evidence that could be achieved.

It was noted if the purpose of the investigation was to search for seasonal variation, or if this variable was a smaller part of a larger investigation having another purpose.

3 RESULTS

We identified 9 publications from the period before 1958, and 4 after 1958, which respected our study criteria (see Figure 1).

Flowchart review procedure

Searching in EMBASE and BIOSIS led to no further publications of interest. No match was found by searching in the Cochrane library.

Tables 2 and 3 highlight the results from the included papers and the type of Cochrane ranking.

TABLE 2. Results, Northern and Central European Studies before 1958, distribution of psoriasis relative to season in percentage Author, year, country Sample size Measure Winter Spring Summer Autumn Method rankinga Nielsen19 1892, Denmark 782 Cases treated 29.5 22.1 21.5 26.9 Vb 77 Disease onset 35 23.4 23.4 18.2 Vb 242 Deterioration 28.1 22.3 26.5 23.1 Vb Krekeler26 1912, Germany 398 Cases treated 28 29 23 20 Vb Hanse23 1916, Germany 241 Cases treated 31 24 25 20 Vb Haxthausen18 1924, Denmark NA Clinic visits through 10 years Month of first visit was equally distributed throughout the year. Vc Hoede24 1927, Germany 154 Disease onset 22 30 21 27 Vb Deterioration 37 25 23 14 Hahnemann21 1932, Germany 470 Cases treated 23 26 29 22 Vb Müller22 1933, Germany 542 Cases treated 30 24 22 24 Vb Steinke25 1935, Germany 6708 Cases treated 24 26 25 25 Vb Disease onset 25 27 21 27 Vc Weinsheimer20 1937, Germany 902 Cases treated 32.5 26.5 19.4 21.7 Vb 333 Deterioration 22 38 21 19 Vc aCochrane ranking of studies described in methods and materials, expressed in roman numbers. V: case series >10 patients, b: cases with measurable objective endpoints (quantitative), c: cases with a personal interview by the investigator (qualitative). TABLE 3. Results, Northern and Central European Studies after 1958, distribution of psoriasis relative to season in percentage Author, year, country Sample size Measure Winter Spring Summer Autumn Method rankingb

Lomholt12

1964, Faroe Islands

206a Improvement 21 1 63 15 Vc Deterioration 25 52 15 8

Hellgren9

1964, Sweden

255a Improvement 28.7 NA 22.6 NA Vc

Könönen28

1986, Finland

1516 Deterioration 54 18 2 NA Vd

Knopf5

1989, Germany

390 Improvement NA NA 60.5 NA Vd Deterioration 37.4 42.3 NA NA aOnly 50% of the interviewed patient experienced seasonal variation. bCochrane ranking of studies described in methods and materials, expressed in roman numbers. V: case series >10 patients, c: cases with a personal interview by the investigator (qualitative), d: cases based on questionnaires (qualitative). 3.1 Studies from before 1958

In the case series with measurable endpoints, several factors have been used to describe seasonal variation. Haxthausen18 used the month of the first visit, Nielsen19 and Weinsheimer20 the number of treated patients each month. The relative distribution of clinical visits was another measure of seasonal variation.21-26 Although there might be some smaller variation among studies, showing a higher prevalence of psoriasis during winter, the overall tendency was close to equal distribution throughout the year.19, 20, 23 In research of more qualitative measures, where the subjective perception of exacerbation of psoriasis is recorded, the results were quite the same.19, 25, 26

In studies before 1958, there was no direct positive evidence for any seasonal variation of psoriasis27; however, Table 2 shows slightly more treated patients and disease onset during winter, and higher rates of deterioration during spring.

3.2 Studies from after 1958

To study the subjective perception of the seasonality effect, Lomholt12 examined and interviewed all psoriasis patients in the Faroe Islands, and Hellgren9 interviewed psoriasis patients from the Department of Dermatology, Gothenborg, Sweden. In both cases, the number of patients experiencing no seasonal variation was about 50%. Of those who felt some kind of seasonality, summer seems to be the season for improvement12, 9 and spring the time for worsening.12 Knopf stated that 60% have summer improvement.5 Contradictory, Hellgren9 observed a decline in disease onset during winter. He found fewer reported exacerbations in the winter months as well as April, May, July, and November, and more in March, June, August, September, and October. Könönen28 reported that 54% of the most widespread activity was seen in the winter and only 2% in the summer, yet he also pointed out that a relatively high number of patients did not have any seasonal variation (see Table 3).

4 DISCUSSION

In the present review, the literature from before 1958 was considered more powerful in the study of spontaneous psoriasis not influenced by modern therapies. It appears from Table 2, including nine studies, that no convincing seasonal variation of psoriasis had been noted. In most cases, only hard measurable endpoints were used. However, from the old studies, it is not possible to deny a small statistical variation of seasonality in the direction of improvement in the summertime.

In the literature after 1958, only four studies were detected, however including self-reported subjective assessments. Studies indicated seasonal variation in about half of the patients with improvement in the summer and possibly the autumn as the general trend. Interestingly, most authors agree that a smaller percentage directly experiences worsening in the summer. Using patient interviews or questionnaires in the more recent studies seem to confirm that there is clinically significant summer improvement.

Studies from outside Northern and Central Europe (see Table 4) agree that many patients have no or little seasonal variation, but many also have an improvement in the summer and a smaller group worsening. Improvement is supposed to be related to the sun. Improvement during summertime is in the global studies a consistent finding.

TABLE 4. International studies after 1958 from outside Europe Author, year, country Sample size Methods Results

Lane29

1973, USA

231 Retrospective study of clinic visits over 2 years. Reported seasonal influence

25% no seasonal influence

60.2% improvement in summer

14.3% deterioration in summer

Farber11

1974, USA

5600

Questionnaire

47% response rate

80% positive effect of sunlight

78% positive effect of warm weather

Bedi30

1977, India

162 Interview, clinic visits over a period of 2 years

54% no seasonal variation

25% deterioration in winter and improvement in the summer

Park10

1998, South Korea

870 Questionnaire

59% improvement in the summer

41% stationary/deterioration in the summer

65% deterioration in the winter

35% stationary/better in the winter

Hancox31

2004, USA

NA Clinic visits over a period of 8 years

Astronomical calendar: Seasonal variation is not significant p = 0.07 (Winter: 30.6%, Spring: 28%, Summer: 20.3%, Autumn: 20%)

Meteorological calendar: Seasonal variation is significant, p = 0.006 (spring 33.8%, fall 20.3%)

Balato32

2013, Italy

300 Consultation

69.4% improved in summer, 13.2 deterioration

8.3% improved in autumn, 31.4 deterioration

1.6% improved in winter, 59.5% deterioration

15.7% improved in spring, 23.1% deterioration

Kubota33

2014, Japan

565 903

Use of healthcare service

Japanese National Database

–0.3% (−0.5 to −0.1%) in hot season referenced to cold season

Minimal seasonal difference

Ammar-Khodja,34 2015, North Africa 373

Consultation

Interview

43% seasonal variation, not specified

79.4% stress as trigger of outbreak

Kimball35

2015, USA

5468

Consultation

Disease score

16% visits in summer

25% visits in fall

31% visits in winter

28% visits in spring

20.4% cleared in summer

15.3% cleared in winter

Harvell36

2016, USA

223

Skin samples

Pathology bank

Histology

15-year retrospective

study

No seasonal variation

Brito37

2018, Brazil

155 Hospitalizations dermatology ward

19% in summer

30% in autumn

27% in winter

25% in spring

Wu38

2020, China

NA

Google Trend Infodemiology data

from Australia, New Zealand vs.

USA, Canada, UK, Ireland, 2004–2018

Small but significant summer/autumn improvement in all countries

Seasonal change followed the climate on the respective hemisphere

The authors’ descriptions of seasonal variation indicate individual traits. Ethnicity and melanin pigmentation, of course, are bound to the person. The relation between Fitzpatrick skin type and seasonal variation seems not studied. Psoriasis patients are of different diagnostic types with individual characteristics relative to severity, outbreaks and, response to treatment. It is likely that seasonal influence on psoriasis also could be a personal characteristic. Following this view and guided by the literature review there may be different characteristic subsets of patients to season, for example, a larger group of about 50% of patients who are not influenced by season, a significant group who are improved in the summer, and a smaller group who do better in the winter. Some in the latter group directly are intolerant to the sun and experience a significant worsening in the summer. D-vitamin levels are reduced in patients with psoriasis and arthritis but independent of season and latitudes, thus, seasonal variation in different subsets of psoriasis patients is unlikely to be attributed to the variable synthesis of D-vitamin in the skin due to variable seasonal exposures to sunlight.39, 40

The concept of subsets of psoriasis patients relative to season automatically shall have implications for UVB therapy: Those with an improvement of psoriasis in summer are possible success candidates. Those with no seasonal variation may gain benefit from UVB, and those with worsening in summer may experience negative effects. A search of the literature has detected no precise study using seasonal variation as a measure of the UVB effectiveness on psoriasis. Climatotherapy given as a 4-week intensive course at the Dead Sea in Israel is highly effective in nearly every patient selected for this treatment and a highly relevant experimental study on the effect of concentrated summer on psoriasis.41-45 Climatotherapy also incorporates relief from stress and illustrates a combined effect. Thus, patients belonging to the subset of no seasonal variation under temperate climate conditions at home may when exposed to the Death Sea climate with aggressive use of sunlight experience major improvement or clearing, at the level of effectiveness from modern biologics.

This study of the literature suffers from limitations that it could not identify or eliminate the potential influence of mood, psyche, and SAD related to the season, which possibly influences the grade of psoriasis during seasons. Numerous other confounders are related to summers such as holidays, travels to other climate zones, leisure, and pleasant feel supporting mental well-being ameliorating psoriasis.

In conclusion, the classical literature on psoriasis and season collected before modern therapies were introduced indicated no seasonal variation of psoriasis. Recent literature limited to Northern and Central Europe indicates that the seasonal effect on psoriasis has three clinical subsets: About 50% are not influenced by season, approximately 30% improve during summer, and about 20% do better in winter. A smaller group becomes significantly worse in summer. Changes of psoriasis relative to season shall be considered as an individual patient characteristic that may guidance the success of UVB light therapy. Observations from Europe are accordant with global observations covering different ethnicities and the northern and southern hemispheres and different climate extremes.

REFERENCES

1Ameen M. Genetic basis of psoriasis vulgaris and its pharmacogenetic potential. J Eur Acad Dermatol. 2005; 153: 346– 51. 2Gudjonsson JE, Elder JT. Psoriasis Epidemiology. Clin Dermatol. 2007; 25: 535– 46. 3Plunkett A, Marks R. A review of the epidemiology of psoriasis vulgaris in the community. Australas J Dermatol. 1998; 39: 225– 32. 4Schäfer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology. 2006; 212: 327– 37. 5Knopf VB, Geyer A, Roth H, Barta U. Der Einfluss endogener und exogener Faktoren auf die Psoriasis Vulgaris –eine Klinische Studie. Dermatol Mon Schr. 1989; 175: 242– 46. 6Griffiths CEM, Richards HL. Psychological influences in psoriasis. Clin Exp Dermatol. 2001; 26: 338– 42. 7O´Leary CJ, Creamer D, Higgins E, Weinman J. Perceived stress, stress attributions and psychologic