Epidemiology and pathogenetic mechanisms of polymorphic light eruption
Janssens, A.S.
Citation
Janssens, A. S. (2008, January 17). Epidemiology and pathogenetic mechanisms of polymorphic light eruption. Retrieved from https://hdl.handle.net/1887/12576
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1
Introduction
Chapter 1
10
Introduction
The research described in this thesis was initiated in 2002, when our group became member of the so-called SUNALL consortium. This was a multidisciplinary group of scientists from six different European countries interested in the pathogenesis of polymorphic light eruption (PLE). The scientific collaboration was funded by the European Commission. The main goal of the joint projects was to shed more light on pathogenetic mechanisms of PLE, but also to provide epidemiologic data, clues on mechanisms of (photo-) therapies and tools to improve diagnosis. A prerequisite was that all parties agreed on a definition of the studied subject. The clinical members of the SUNALL consortium reached consensus that polymorphic light eruption (PLE) is primarily a recurrent pruritic eruption comprising papules and/or vesicles and/or plaques, which occur on sun exposed skin sites, and which heal without scarring. We agreed to include patients with a classical history of PLE who also had positive ANA antibodies. However, the presence of antibodies against SSA and SSB was accepted as an exclusion criterion. Eczematous sun-induced lesions were not regarded as PLE.
In this introduction, recent insight into epidemiology, pathogenetic mechanisms, photo provocation procedures, differential diagnostic aspects and treatment of PLE are discussed, and questions addressed in this thesis are formulated.
Epidemiology
The term polymorphous light eruption was first used by the Dane Rasch in 1900. 1 Before that time, several names were used to describe this idiopathic photodermatosis, such as eczema solare, summer prurigo, summer itch, solar dermatitis and benign summer eruption. PLE is the most common idiopathic photodermatosis. Epidemiological data on PLE are sparse, but the prevalence is estimated to be around 10-20% in the USA, England and Ireland. 2
The male/female ratio varies between 1:2 and 1:4 and the disease occurs preferentially in young women. Underlying genetic and/or hormonal differences together with the difference between women and men in seeking medical attention for dermatological problems seem to be likely causes of this gender difference. 3 A contributing role of the female sex hormone 17-oestradiol has been investigated to explain the gender differences of PLE. The role of 17-oestradiol on immunosuppression and contact hypersensitivity (CHS) caused by ultraviolet B (UVB) irradiation, was investigated in male mice intraperitoneally injected with the hormone and in female mice treated with anti-estradiol. 4 The results suggested that 17-oestradiol prevented UVB-induced suppression of the CHS response caused by lower concentrations of immunosuppressive cytokines (IL-10) produced by keratinocytes. Hormonal contraceptives can induce photosensitivity and are
very widely used by women. These hormones could, as an exogenous factor, contribute to this female dominated prevalence of PLE. 5;6
Two studies based on interviews, conducted in the USA by Morison and Stern and in Sweden by Ros and Wennersten, have made clear that only 3-15 % of the responders with a history consistent of PLE, sought medical attention. 7;8 These surveys indicate that the prevalence of PLE is probably much higher than normally reported. PLE has a wide geographical distribution and it is believed to be more frequent in temperate than tropical climates. 9 In another epidemiological study, the prevalence and clinical characteristics of polymorphic light eruption were assessed by a questionnaire survey among 172, 196 and 182 subjects in Perth, Ballarat and London, respectively. The prevalence was 5.2% in Perth (latitude 32 degrees), 3.6% in Ballarat (37.5 degrees) and 14.8% in London (51.5 degrees). The age of onset (mostly diagnosed in the first three decades) and male/female ratio (1:3) were similar in all three areas. Development of tolerance during the summer was more common in Perth (66.7%) and Ballarat (71.4%) than in London (40.7%). 9
PLE is mainly a disease affecting the fair-skinned population. It is also believed that PLE occurs mainly in UV-unadapted skin. A study conducted among tourists visiting Hawaii illustrated that the cutaneous disorders of the Caucasian island visitors differed significantly from those observed in the local population. In the visitor group, over one-third of the diagnoses were light-induced conditions.
The most common disease observed was the papulovesicular variant of polymorphous light eruption. 10 In another 10-year study conducted in Nigeria, light-sensitive dermatoses appeared not to be common among the black people.
Only 64 cases (about 0.4% of all dermatological patients) had light-sensitive dermatoses. Two patients with polymorphic light eruption were visiting Caucasians. 11
Outline 1
To improve on the available epidemiological data, the SUNALL consortium has conducted a questionnaire survey among 6,895 individuals in 6 different European countries. We investigated the prevalence of PLE and its dependence on geographical latitude, gender, occurrence during springtime or sunny holidays and skin type. This survey is described in chapter 2.
Aetiology and pathogenetic mechanisms of PLE
The rash of PLE is induced by exposure to ultraviolet radiation (UVR). The evoking wavelengths apparently vary between patients, but typical lesions occurred following irradiation with broadband UV-B lamps (290-320 nm), UV-A (320-400 nm) or solar simulated radiation.12-16
Verwijderd: Chapter
Chapter 1
12
Normal UV-induced immune reactivity
Our knowledge and understanding of the effects of UV radiation on human health and topical effects on the skin comes from studies that combine elements of photobiology, immunology and dermato-oncology. From photoimmunological investigations it is recognized that UV irradiation suppresses cutaneous T-cell- mediated immunity in humans. 17 Most studies used the contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH) responses to a variety of sensitising agents (such as di-nitrofluorbenzene (DNFB)) as a model to study the effects of UV radiation on immune responses. 18;19 In the CHS reaction, a hapten is applied onto the skin, and antigen-presenting cells (APC), mainly epidermal Langerhans cells (LC) take up the antigens and migrate to regional lymph nodes, where they interact with naïve T-helper cells to initiate the response. After expansion and differentiation, the T cells enter the circulation and upon a next contact with the same antigen on the skin, they cause local CHS response with symptoms of redness, itching and swelling. The DTH response is similar, except that the antigen is introduced by the intradermal or subcutaneous route. The initiation of UVR-induced immune suppression of the skin is accompanied by depletion of epidermal LCs, dermal and epidermal influx of CD11b+ neutrophils and macrophages and release of cytokines, in particular interleukin 10 (IL-10). 18;20 UVR-induced immune suppression of CHS and DTH responses is achieved by a single or repeated low-dose UVB irradiation before the application of the antigen, leading to an absence of a visible response and possibly to tolerance to this antigen.
These immune suppressive responses take place in every healthy person.
UV-induced suppression of cellular immunity can be thought of as a sound physiological reaction. What if the above mechanisms become disturbed or diminished? It is hypothesized that an imbalance of UV-induced pro-inflammatory reactions and immunosuppression could lead to a pathological skin reaction to a UVR-induced antigen (photoantigen), and that a UV-induced allergy e.g. PLE could develop.
Prior histological examination of PLE lesions revealed some features that were also found in DTH responses, such as the expression of intercellular adhesion molecule-1 (ICAM-1) and upregulation of major histo-compatibilty complex class II (MHC class II) on keratinocytes. 16 Also, the switch from a predominance of CD4+
lymphocytes in infiltrates of new PLE lesions to a predominance of CD8+
lymphocytes in older PLE lesions 13 resembled the change observed in a DTH response.
To unravel early pathogenetic mechanisms, other investigators focused on the pre-lesional UV-triggered skin responses in PLE patients. In 1999, Kölgen and co-workers reported that epidermal LCs of PLE patients persisted in the epidermis upon a high dose of UVB irradiation. 21 That contrasted with the depletion in healthy subjects. Other investigators reported that CD11b+ macrophage-like cells
Introduction | 11
infiltrate the epidermis 48 and 72 h after UV exposure in skin of healthy individuals. 19 The authors suggested that the ability to induce locally a state of in vivo tolerance is closely associated with the expansion of class II MHC+/CD11b+
monocytes/macrophages in the dermis and epidermis. 19 Kölgen et al. showed that these CD11b+ cells infiltrated the epidermis in PLE patients in lower numbers than in healthy control subjects upon a single high UVB exposure and that these cells were in fact neutrophils. 22 Furthermore, the neutrophils displayed cytoplasmatic expression of IL-4, IL-10 and TNF-D. 22
TNF-D and IL-1D have been linked to UVR-induced migration of LCs 23, and IL-10 to impaired antigen-presenting function of LCs. 24 IL-12 disposes the skin toward development of a Th1 response that is crucial for the induction of contact hypersensitivity, and it can abrogate the immunosuppressive effects of UVR. 25 However, no abnormalities were observed when measuring mRNA levels of TNF- D, IL-1D, IL-10, and IL-12 in skin of PLE patients, at 6 and 24h after low dose solar simulated radiation (SSR) exposure.26
Two studies have been conducted to test functionally the hypothesis that UVB-induced immunosuppression fails in PLE. Van de Pas et al. tested PLE patients and showed that in contrast to healthy controls, a single dose of UVB radiation around 1 MED failed to suppress CHS in these patients. 27 Similarly, Palmer and Friedmann found that the induction of sensitisation to 2,4- dinitrochlorobenzene was less suppressed by UVR in PLE patients than in healthy controls. 28 These investigations confirm the hypothesis of failing UVB-induced immunosuppression in PLE patients and have thus contributed considerably to the clarification of some pathogenetic mechanisms in PLE.
Thus, the lower depletion of LCs and decreased infiltration of neutrophils together with a possibly disturbed cytokine expression and an unsuppressed CHS response after UV exposure are indicative of an imbalance of UV-induced immune responses in the skin of PLE patients as compared to healthy controls.
Outline 2
Inchapter 3, 4 and 5 of this thesis, we describe three investigations to unravel the pathogenetic mechanisms of PLE: We have investigated whether the lower UV- induced epidermal LC migration and neutrophil infiltration was specific to PLE, or occurred also in a group of patients with photosensitive lupus erythematosus (LE).
This would give evidence for a shared pathogenetic mechanism of photosensitivity in PLE and LE. The results of this study are described in chapter 3.
Furthermore, we wondered whether the supposed imbalance of UV-induced immune cell responses in PLE would shift towards a normal situation after a course of UVB therapy (chapter 4). A normalisation of cell responses in PLE
Chapter 1
14
patients after UV hardening would support a role of these cells in pathogenetic mechanisms of PLE.
The last research question was whether UVB irradiation would change the cytokine profile of PLE skin in such a way that it could explain underlying mechanisms of the impaired LC migration and neutrophil infiltration or of pro- inflammatory responses. We expected to observe lower concentrations of LC and neutrophil recruiting cytokines. The results of this investigation are described in chapter 5.
Clinical features of PLE
The appearance of PLE lesions is polymorphic. It ranges from papulo-vesicular lesions to multiple small and large papules that can coalesce to form plaques. 2;29 The lesions are moderately to severely pruritic, last for several days to weeks and heal without leaving scars. They mainly appear on sun-exposed skin areas, several hours to a few days after exposure. 2 Predilected areas are the neck, upper chest, dorsa of the hands, dorsolateral aspects of the upper arms, the legs and dorsa of the feet. In some patients, the process may generalize, with more severe lesions on photo-exposed sites. Flares of previously affected areas may occur when other parts are exposed to the appropriate radiation from the sun or artificial sources. 2
The time of sun exposure, necessary to induce PLE lesions, can vary from several minutes to several hours, sometimes on consecutive days. It would normally take one or two days after first sun exposure for the rash to appear, but appearance after some hours is also possible. If further exposure would be avoided from the beginning of the rash, lesions will resolve spontaneously after some days or some weeks. Since complete avoidance of sun exposure is not always possible, the lesions may stay on the skin for up to 6 months during spring and summer time. The lesions mostly emerge at the beginning of springtime when the first intense sunrays appear. In the course of the summer, a gradual waning of lesions can be observed, as a result of UV-adaptation. 30 The time course of symptoms is likely to be dependent on geographic and climatologic factors. PLE has a chronic intermittently relapsing course. In different long-term follow-up studies spontaneous remission was reported in 11-23% after 7-32 years. 30;31
Figure 1. PLE lesions on the upper chest, one of the predilected areas
Introduction | 13
Differential diagnosis of PLE
PLE should be differentiated from photosensitive disorders like actinic superficial folliculitis 32, acne aestivalis, solar urticaria 33;34, photocontact dermatitis, phototoxic reactions, photosensitive eczema 35, hydroa vacciniforme and erythropoietic protoporfyria. Table 1 gives an overview of the most important differential diagnoses of PLE.
Distinguishing PLE from subacute cutaneous lupus erythematosus (SCLE), chronic discoid lupus erythematosus (CDLE) and photosensitive LE is sometimes very difficult and can remain a problem throughout the whole time course of the disease. Therefore, the clinical features of these two diseases are given in more detail.
SCLE and CDLE
Previously, PLE was thought to be associated with lupus erythematosus (LE) but these diseases are now considered two distinct entities. 2;30;31 Skin lesions are found in up to 90 % of patients with systemic LE. 37 There is a clear relationship between sunlight and the manifestations of cutaneous LE. Up to 73 % of patients with systemic LE report photosensitivity. 37 Typical LE lesions occur on the face, the conchae of the ears and upper chest. They appear as round-oval or polycyclic erythematous plaques or annular lesions and after healing they leave central scars and atrophy.
Differentiation between PLE and LE is of high importance as desensitisation or UV hardening with PUVA or UVB is contradicted in LE. Antibodies to ENA, anti- Ro and anti-La are strongly associated with LE and SCLE, but not with PLE, and are therefore helpful in distinguishing between these disorders. The histology of
Chapter 1
16
SCLE may look identical to PLE but the follicular plugging and epidermal atrophy are important signs that only occur in SCLE and CDLE. Direct immunofluorescence may show IgG and IgM deposits scattered along the dermo- epidermal basement membrane zone in CDLE. It has been shown with photoprovocation tests in photosensitive LE patients that both PLE- and LE-like lesions can be induced with UV radiation. 38 Thus, the outcome of phototesting will not always lead to a better distinction between PLE and LE. Therapeutic possibilities for photosensitive cutaneous LE are to some extent similar to PLE, except for the artificial and natural hardening, which are contradicted in LE.
Diagnostic procedures of PLE
Diagnosis of PLE is based mainly on a combination of history taking and clinical symptoms. The definition of PLE as used in our studies is given in the introduction.
In some cases, it is desirable to perform provocative phototesting to reproduce the photodermatosis in a controlled clinical setting.
Phototesting
Great variations in methods, UV-sources, irradiation protocols and positive reactions to provocative phototesting have been described since the early 80's.
Percentages of positive photo-provocation tests range from 48 to 100%. 12;15;39-47
Unfortunately, descriptions of the evoked skin rash after the provocation, are frequently absent. This in particular is very important for confirmation of the diagnosis. In contrast to former believe, there appears to be no difference in the ease of provocation between previously affected skin and previously unaffected skin of PLE patients. 15 In accordance with the protocol of SUNALL group, the provocation tests at our department are performed on a non-suntanned, non- lesional skin area on the flexor side of one forearm with a standardised dose of 20 J/cm2 UVA (Cleo Performance lamps).
Although > 95% of the UV output stems from the UVA band, it is important to note that 50% of the erythemal effective dose stems from the UVB band. The other arm is tested with 1 MED of UVB (TL12 lamps). The provocations were repeated on consecutive days, up to a maximum of three days. Reading is done 24 hours after every irradiation until a rash appears. An erythematous reaction with papules, plaques or vesicles is regarded a positive provocation and is suggestive of PLE. It is important to ask the patients about the resemblance between the provoked rash and the rash for which they sought medical attention.
Artificially provoked lesions are always milder than the naturally occurring ones.
The appearance of heavy sunburn, an eczematous rash or pustules does not support the diagnosis of PLE. The most suitable season for testing is assumed to be winter or early springtime, when environmental sunlight radiation is low and UV-adaptation is absent.
Introduction | 15
MED testing for UVB was performed using a device, first described by Diffey et al. 48 As depicted in Figure 2, we have adjusted this device for application onto the skin. The device contains ten holes with perforated meshes, with increasing permeability. In this way, a single UV irradiation will produce a UV range of 1:8 from the least permeable to the highest permeable hole, each subsequent hole increasing with a step of 26%. This tool for MED testing is used for most of our studies. An MED test range is also shown in figure 2.
A recent study suggests that high severity of the disease correlates with a positive outcome of UV-provocation testing. 49 However, this has never been tested in a large group of patients.
Outline 3
Inchapter 6 we have investigated whether a severity score of PLE correlates with the outcome of UV provocation testing. We expected to find the highest severity scores in UV-A and UV-B susceptible patients. The provocation outcome would then be a reliable tool to predict the severity of PLE. This could also be of significance for the therapeutic advice to individual PLE patients.
Table 1. Differential diagnosis of photodermatoses
Diagnosis Age of onset Aetiology & frequency Clinical features
Polymorphic light eruption adulthood idiopathic; very common Papules, vesicles, plaques on all UV-exposed areas.
Starts 24-72 hours after UV-exposure; lasts 1-2 weeks, but can stay several months due to repeated UV-exposure.
Actinic superficial folliculitis adolescence &
adulthood
Idiopathic; very rare Folliculitis on upper extremities and trunk.
Starts 24-72 hours after UV-exposure; lasts 2 weeks.
Acne aestivalis adolescence &
adulthood
idiopathic; history of acne vulgaris; very rare
Papules, pustules and comedones on the face Starts 15-30 days after sun exposure; lasts 6 months Solar urticaria any age idiopathic; very rare Urticaria, can occur on the whole body.
Starts within minutes after sun exposure; lasts max. 24 hours Photocontact dermatitis mainly adulthood chemical-induced delayed
type contact
hypersensitivity; common
Eczematous lesions, localisation depends on the application site of the chemical and on sun exposed areas.
Starts 24-72 hours after sun exposure; lasts 2 weeks or several months.
Phototoxic dermatitis mainly adulthood drug-induced;
common
Presents as heavy sunburn, on all sun exposed skin sites; starts within few hours after sun exposure; can last several days or months with repeated exposure.
Hydroa vacciniforme childhood idiopathic; very rare Burning papules, bullae and crusts, on nose, distal limbs, leaving pock scars.
Starts within hours, lasts several days.
Erythropoietic protoporphyria
childhood inherited metabolic disorder of haem
synthesis; rare
Painful vesicular lesions, on nose, cheeks, fingers, leaving pitted scars.
No protection from window glass.
Starts within minutes, lasts a few days Photosensitive eczema any age idiopathic, history of atopic
eczema; rare
Severe sun sensitivity and triggering of atopic eczema.
Symptoms are mostly present year round with flare-ups during the summer Actinic reticuloid mainly adulthood idiopathic; very rare Persistent infiltrated papules and plaques on light-exposed skin, often with
extension to covered areas or generalised infiltrated erythroderma; lymphoid infiltrate that resembles mycosis fungoides and is dominated by atypical CD8+
cells. 36 Chronic actinic dermatitis mainly above 50
years
idiopathic; rare Mainly affecting men. Chronic eczematous lesions with no clear seasonal dependency. Patients suffer from extreme photosensitivity, sometimes even to visible light. Associated with multiple contact allergies.
Introduction | 17
Chapter 1
18
Figure 2 MED testing device (A) and MED test (B)
A
B
Histo-pathology
Histo-pathological examination of PLE lesions is only partly helpful in establishing the diagnosis of PLE. The characteristic features of PLE lesions include epidermal changes of variable intensity, such as parakeratosis, focal spongiosis and vacuolar degeneration of basal cells. In the dermis, a superficial and deep perivascular lymphocytic infiltrate with subepidermal edema is seen. In a papular PLE lesion, these features are most prominent. The morphological variants of PLE are characterised by the same histological pattern, although additional features may be present. For instance, in the vesiculo-bullous form of PLE, spongiotic vesicles and severe subepidermal oedema that leads to blister formation are present. 50
In experimentally provoked lesions, intercellular adhesion molecule I (ICAM-I), human leucocyte antigen class II molecule (HLA-DR) and OKM5 expression were found on keratinocytes in a high number of PLE patients. This contrasted with healthy individuals, in whom the antigens where not expressed. 16 These antigens are commonly considered to play a role in antigen presentation and elicitation of an immune response. 51;52 PLE displays an accumulation of CD4+ T cells within hours and CD8+ T leucocytes within days after sequential UVR exposure, a picture that mimics delayed type hypersensitivity reactions. 13;16 These observations support the theory of an immunological basis for PLE.
Serologic antibody testing
PLE can precede, coincide or overlap with photosensitive lupus erythematosus. It is therefore recommended to test for the presence of anti-nuclear antibodies (ANA) and more particularly antibodies against extractable nuclear antigens (A- ENA, anti-Ro (SSA) and anti-La (SSB) antibodies) in any patient with a presumed photosensitivity disorder. 53 As mentioned earlier in this introduction, a classical history of PLE, but with the presence of A-ENA was regarded an exclusion criterion in our studies. PLE patients with positive ANA serology, without other criteria suitable to the diagnosis of LE were regarded as having PLE and were included in our studies.
Treatment of PLE
Therapeutic possibilities are limited and only partly effective. Treatment is generally aimed at preventing the disease. A summary of therapeutic options of PLE is given in table 2.
Prevention
Patients are not advised to strictly avoid sun exposure, but to expose themselves for some minutes in the morning or the end of the afternoon, starting in early springtime under mild conditions. 54 This results in an adaptation of the skin to natural sunlight (so-called hardening). It is advisable to increase the sun exposure with 15 to 30 minutes per day each week. A useful tool for the patient is to keep a diary, to note down sun exposure time and any rash that occurs during hardening.
This will increase the patients' understanding and confidence of the effects of sun exposure.
The use of sunscreens with high sun protection factors (SPF) seems a sound advice but can be misleading, since most of the sunscreens protect mainly against UVB, while UVA is also responsible for triggering PLE. Sunscreen use can even lead to exacerbation of PLE. 55 It has been shown that photosensitive patients fail to apply sunscreen in some prominently exposed sites and use less sunscreen than recommended by the manufacturer (2 mg/cm2). As a result of that, the degree of
Introduction | 19
Table 2. Therapy of PLE
Treatment Period Dose Duration Side effects Advantage Disadvantage
Natural hardening Early spring and summer
Start with 10- 20 minutes twice daily, increment with 5-10 minutes
Whole sunny season
PLE rash Prevention.
No hospital consultation
Highly dependent on local weather conditions
Artificial hardening Early spring Starting dose 0.1 MED incremented with steps
6 weeks Sunburn, PLE rash
Prevention Often regarded as time- consuming
Hydroxy-chloro- quine
Early spring and summer
200 mg 1dd 7 months Oculotoxicity Prevention. Lower tendency to sunburn Sun protection
creams
Early spring and summer
> factor 20 7 months Effect on immune system unknown
Prevention.
Increases sun exposure time
Prevents UV-hardening
Clothing Early spring and summer
Hat, long sleeved shirt, trousers
No Prevention.
Increases sun exposure time
Prevents UV-hardening.
Rash can appear on body parts despite clothes.
Undesirable with hot weather
Topical steroids When rash appears
Class 3 or 4 steroid
2 weeks No Downregulation of
inflammation
Only symptomatic, not always effective Antihistamines When rash
appears
By doctor's prescription
2 weeks Sleepiness Decrease of some itch
Only symptomatic, not always effective Systemic steroids With severe
rash
30 mg Usually 3-
5 days
Infection Quickly effective.
Can also be used as preventive measure
Systemic side effects of corticosteroids
Chapter 1
20protection is much lower than anticipated from the stated SPF of the product. 56 Moreover, stringent use of sunscreens will hamper UV hardening of the skin.
Protective clothing can mostly prevent the development of skin lesions, but it is not always desired during sunny and warm days.
Artificial hardening can be achieved by serial and gradually increasing whole-body irradiation with UVB lamps or psoralen plus UVA (PUVA) for two times a week during 6 weeks. 57 This results in diminishing of symptoms but it should be repeated every year in the beginning of springtime. Without regular sun exposure after PUVA therapy, patients were shown to lose their photoprotection after 4-6 weeks. 58 Rucker and co-workers compared the effect of UVA lamps in a clinical setting with sunbeds and concluded that the use of sunbeds in well equipped tanning studios with appropriately educated staff is also a reliable setting for hardening therapy. 59 In a questionnaire among 68 Dutch PLE patients who received PUVA hardening for five years, 55% reported great benefit from the therapy, 34% noticed some improvement and 9% had experienced no benefit or even worsening of their symptoms. The symptom-free interval after PUVA hardening was longer than 6 months in 38% of patients and between one and six months in 15% (unpublished data). On average, patients who stated to benefit from PUVA therapy tended to use sunscreens with a lower SPF than patients who had experienced no effect. Artificial hardening was considered a burden by 60% of the responders.
Symptomatic approach
The skin lesions of PLE can be treated with moderate or potent topical steroids.
Indications for the use of hydroxychloroquine are insufficient effect of sunscreen preparations and failure of UV hardening. 60 Hydroxychloroquine can be given in a starting dose of 400 mg and a maintenance dose of 200 mg daily. The mechanism of action is unknown but this treatment results in a moderate reduction of skin rash and it has anti-inflammatory properties. Somewhat paradoxically, hydroxychloroquine can also induce photosensitivity. However, this is regarded a side-effect which occurs only in a few patients and with high dosages. Chloroquine is not an obligatory phototoxic drug. Oculotoxity may be a serious side effect of this treatment and therefore, yearly ophtalmologic check-up is advisable when daily doses higher than 200 mg per day are used.
Conclusion
Polymorphic light eruption is the most common photodermatosis with an unknown etiology. The course of the disease is intermittently recurring and it can persist for decades. The minority of the patients suffer from severe complaints that affect their normal daily lives. Differentiating PLE from photosensitive cutaneous LE can be difficult, the disorders can even co-exist. The therapeutic and diagnostic
Introduction | 21
Chapter 1
22
options in this photodermatosis remain limited as a result of its unknown pathogenesis.
Therefore, further clinical and immunological research should also be aimed at improvement of the therapeutic and diagnostic possibilities.
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