A review of UVA-mediated photosensitivity disorders

Abstract

A number of skin conditions are characterised by photosensitivity to UVA. Some of these are exclusively UVA-mediated conditions, while others include UVA in the action spectrum which also include UVB and/or visible light. This review aims to describe this diverse range of conditions for non-dermatologist scientists with an interest in this topic. As such, clinical details, including treatments, are brief and succinct. Recent advances in understanding the pathogenesis of these conditions is highlighted.

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Introduction

Photosensitivity to UVA is common and may arise by a number of different mechanisms. The range of conditions where UVA photosensitivity is implicated include polymorphic light eruption (termed ‘polymorphous light eruption’ in North America), drug-induced photosensitivity, plant-induced photosensitivity (termed “phytophotodermatitis” by dermatologists), solar urticaria and chronic actinic dermatitis. Much rarer conditions where UVA photosensitivity is a feature include hydroa vacciniforme, the Smith-Lemli-Opitz syndrome and actinic prurigo. Additionally, the autoimmune disorder lupus erythematosus is often aggravated by ultraviolet light, including UVA. This review article aims to describe each of these UVA-mediated photosensitivity disorders in order to provide an update on this evolving field of photo-medicine.

Methods

The following search strategy was used:

Medline, Embase, PubMed and the Cochrane Library were searched for the following terms during the period of January 2005 – January 2011:

Photosensitive*

UVA or ultraviolet light or sunlight

Polymorphic light eruption/polymorphous light eruption

Chronic actinic dermatitis

Solar urticaria

Hydroa vacciniforme

Actinic prurigo

Drug-induced photosensitivity

Smith-Lemli-Opitz syndrome

Phytophotodermatitis

Lupus erythematosus

Chronic actinic dermatitis

Chronic actinic dermatitis (CAD) is one of the most severe photosensitivity conditions.¹CAD typically presents in men between the ages of 40 and 80. It is an immunologically-mediated disorder representing a form of delayed hypersensitivity to sunlight-induced endogenous cutaneous allergens.² Despite many clues and much effort, CAD remains an enigma, with a clear understanding of the mechanism underlying this condition still elusive.

CAD is known to be associated with allergic contact dermatitis and outdoor activity. Clinical features include a persistent eczematous change involving sun-exposed and sometimes covered sites. Skin biopsy shows histological features of an eczematous disorder; if severe, this may mimic the appearance of cutaneous T-cell lymphoma, a form of low-grade lymphoma characterised by accumulation of malignant T-cells in the epidermis. Photo-testing in CAD typically reveals marked photosensitivity characterised by reduced minimal erythema doses (MED) to UVA, UVB and/or visible light.

CAD is a chronic disorder. Thus, persistence is common, with probability of resolution being just 50% after 15 years.³ However, most cases improve once the diagnosis has been confirmed and a rigorous photoprotection strategy has been implemented. Protection against the relevant activating wavelengths of UV and visible light is imperative in the management of CAD. Topical steroids are usually required; more recently, the topical calcineurin inhibitors pimecrolimus or tacrolimus have been used.⁴ In severe cases uncontrolled by rigorous photoprotection, oral immunosuppression with corticosteroids, azathioprine, ciclosporin or mycophenolate mofetil may be required.⁵

A recent study from London reported the changing pattern of contact allergens associated with CAD comparing 50 patients attending for patch testing between 2000 and 2005 with 86 attending between 1987 and 1992,⁶ the number with positive results declined from 75% to 64% in that time. Sesquiterpene lactone mix (found in members of the daisy family) was reported as the most frequent contact allergen from this series and was positive in ∼20% of cases. An increase in reactions to p-phenylenediamine (a form of permanent hair dye) was also noted, possibly explained by changing exposure patterns.⁶ Parthenium dermatitis caused by airborne contact with the pollen of Parthenium hysterophorus is becoming an increasingly common trigger for CAD in India.⁷ Treatment of CAD should also include attempts to avoid known contact allergens in addition to the rigorous photoprotection.

Solar urticaria

Solar urticaria (SU) is a rare form of acquired photosensitivity characterised by skin weals (similar to a ‘nettle rash’) within minutes of sun exposure.⁸ SU occasionally includes angio-oedema (swelling of the soft tissues of the face).⁹ This may rarely occur without the more characteristic urticarial weals on non-facial sun-exposed sites.¹⁰ SU is more common in females. The action spectrum for SU typically includes UVA and may also include UVB and/or visible light. The peak age of onset for SU is the fourth or fifth decade.⁸

Mast cell degranulation is a prominent feature of SU; the precise mechanism triggering this response has not yet been identified.¹¹ However, it is likely to be an IgE-mediated response to a photo-induced allergens that is either only formed in patients with SU or formed in normal people as well but only causes an allergic response in patients.¹² The photoallergens can be multiple and have variable molecular weights dependent on the action spectrum of SU.¹³ Other allergic disorders can be associated with SU.¹⁴

The weals of SU typically occur within minutes of sun exposure and is confined to exposed skin only. These urticarial weals characteristically clear within a few hours. Itch is a common and often distressing feature of SU. A minority of patients experience a severe anaphylactoid reaction if large areas of skin are involved. Tolerance to sunlight may occur following cautious incremental sun exposure. However, the rate of spontaneous resolution in one series was just 25% at 10 years.⁸

Management of SU is primarily by non-sedating anti-histamines and photoprotection. Desensitizing phototherapy or systemic treatment is occasionally used. In one study more than a third of patients with SU reported a Dermatology Life Quality Index of greater than 10 (a score of 10 on the DLQI is generally accepted to be a large effect comparable to other severe skin diseases that impact significantly on patient's quality of life).¹⁵

Intravenous immunoglobulin (IVIG), a polyvalent antibody product, has only been reported as a treatment in a small number of SU cases. Although in use for the treatment of immunodeficient, autoimmune and other inflammatory disorders for decades, the precise mode of action of this novel treatment is poorly understood . Recent evidence points towards an increase in the suppression of antigen presentation and B-cell antibody production as well as potential roles in controlling complement.¹⁶ Since IVIG is an infusion of IgG antibodies, it is unclear how this would interfere with SU pathogenesis which is more likely to be IgE driven process. However, mast cell degranulation can involve complement.^17,18 A recent report of two patients with resistant solar urticaria (SU) over at least five years who were given a total dose of 2 g/kg over three days showed transient and only slight subjective clinical improvement. There was no change in the minimal urtication dose (MUD) on repeat photo-testing.¹⁹ This disappointing response contrasts with previous reports for IVIG in SU, although some of these included concomitant treatment with other systemic agents. For example, a Swiss study reported a dramatic improvement in UVA and UVB tolerance in a SU patient following a single course of IVIG (total dose of 2 g/kg) in association with terfenadine (an anti-histamine). Subsequent testing at 100 days post-treatment showed a significant improvement in tolerance.²⁰ Another report of two cases of SU treated with IVIG to a total dose of 2 g/kg over five days achieved complete remission for 13 months and 4 years respectively.²¹

Recent reports of SU treated with the anti-IgE monoclonal antibody omalizumab are based on the theory that SU is an IgE-mediated condition. A 52-year-old woman with severe SU and UVA sensitivity was given 150 mg of omalizumab every four weeks. After the first dose she reported complete resolution of symptoms and at four weeks had normal photo-tests.²² A 16-year-old boy with refractory disease and proven UVA and UVB sensitivity was given 400 mg of omalizumab every two weeks for three months. Testing one week after the 6th dose showed reduced sensitivity to UVA, but no change in responses to UVB.²³

Five SU patients treated with a single dose of 16 mg subcutaneous afamelanotide implant in winter have recently been reported. Afamelanotide is a synthetic, more stable analogue of alpha-melanocyte stimulating hormone. Objective testing of response was by measurement of skin melanin density and repeat monochromator light testing at intervals up to 60 days after treatment. Melanin density peaked at day 15 and remained elevated at day 60. The minimal urtication dose decreased by greater than twofold at day 60 (300–600 nm); there was also a significant decrease in weal area.²⁴

Hydroa vacciniforme

Hydroa vacciniforme (HV) is one of the rarest photosensitivity disorders; it tends to occur in children in their early teens.²⁵HV is characterised by sun-induced blistering, inflammatory skin lesions on exposed skin. These tend to form haemorrhagic crusts persisting for many days before healing occurs with scarring. The pathogenesis of HV remains unknown. Phototesting in HV is often normal. However, when an abnormal reaction occurs, it is to either monochromatic or broad-spectrum UVA.^25,26 Clinical lesions tend to appear within hours of exposure to summer sun over the face and/or other exposed sites and are recurrent. Initially these consist of pruritic macules which develop into vesicles or blisters; crusting and vacciniform-scarring is the usual outcome of these acute lesions. Rarely, general malaise accompanies the skin symptoms.

Recent reports on HV have implicated the Epstein-Barr virus as having a causative role in atypical cases, particularly in adults.^27,28 More recently, typical HV persisting into adult life has been strongly associated with Epstein-Barr virus.²⁹ It remains unclear how this viral infection is related to the pathogenesis of the disorder, but accumulating evidence suggests that further study of this topic will provide new insights into HV. There is also evidence that HV-like lesions can progress into malignant EBV lymphoma.^28,30,31

Hydroa vacciniforme is usually hard to treat. Rigorous photoprotection is required until clinical remission occurs. In most patients HV resolves by late teens or the early twenties. In more persistent cases, and in those where adequate disease control cannot be achieved with photoprotection alone, other treatments may be required. Phototherapy with narrowband UVB may be successful in some patients.^25,26 Other treatments occasionally used for HV include oral antioxidants, antimalarials, azathioprine, ciclosporin and dietary fish oil.^26,32–34

Actinic prurigo

Actinic prurigo (AP) is an acquired, immune-mediated photosensitivity disorder. AP typically commences in childhood, but is also seen in adults. It is characterised by the presence of intensely itchy papules, nodules and plaques on sun-exposed sites. AP sometimes arises in a patient with long-standing atopic eczema and may, as a result, go undiagnosed for many years. It often persists throughout the year with exacerbation during the summer months. Indigenous American Indians with AP often have prominent involvement of the lips, eyelids and conjunctivae. AP typically resolves in adults but may sometimes follow a chronic relapsing and remitting course.

Photo-testing in AP may be normal; however, more than half of patients show abnormal reactions to UVA and/or UVB. The strong association for AP with HLA DRB1*0407 found in British patients^35,36 has subsequently been confirmed in Amerindians.^37,38 HLA typing for DRB1*0407 is a useful test in cases where the diagnosis is not clear.

The management of AP is often difficult. Photoprotection is essential in all patients, consisting of behavioural change, use of clothing and sun-glasses; a high SPF sunscreen that protects well against UVA is essential.³⁹ Additionally, topical corticosteroids or calcineurin inhibitors are important, particularly in those with extensive eczematous skin changes. Resistant cases may require narrow-band UVB phototherapy⁴⁰ or PUVA .⁴¹ Systemic therapies are occasionally needed for severe resistant disease; options include thalidomide,⁴²β-carotene, pentoxifylline,⁴³tetracycline,⁴⁴ oral corticosteroids⁴⁵ and azathioprine.⁴⁵ Topical ciclosporin has been reported to treat severe, resistant ocular AP.⁴⁶

Drug-induced photosensitivity

Drug-induced photosensitivity is characterised by an abnormal skin reaction to sunlight after administration of a pharmaceutical agent.⁴⁷ Topical or systemic treatment with medication that is able to absorb UV and/or visible light may lead to photosensitivity reactions in susceptible individuals.⁴⁷ It is now recommended that all drugs that absorb UV and are either topically applied or can reach the skin after systemic treatment should be screened for their photosensitizing potential before they are licensed for human use.⁴⁸Drugs more commonly implicated as causing cutaneous photosensitivity include amiodarone (a drug used to treat cardiac arrythmias), non-steroidal anti-inflammatory drugs (NSAIDs), thiazide diuretics, tetracycline antibiotics, chloropromazine, and fluoroquinolone antibiotics and sulphonamide antibiotics.

Several subtypes of drug-induced photosensitivity are recognised each with different pathogenesis and clinical features; these depend upon the molecular and photophysical characteristics of the drug in question.⁴⁹ Phototoxicity is by far the most frequent mechanism for drug-induced photosensitivity; this can be tested for by use of a volunteer study.⁵⁰ It is caused by UV absorption by the drug leading to an excited state and formation of either free radicals or singlet oxygen that then causes cellular damage.⁵¹ There is no involvement of the immune system. Photoallergy is much less common since it requires the drug to bind to a skin protein before it is capable of eliciting an immunological response. This is usually of the delayed hypersensitivity type.⁵² Rarer forms of drug-induced photosensitivity include pseudoporphyria, photo-onycholysis, dyschromia, lichenoid and telangiectatic reactions.

The most common clinical manifestation of drug-induced photosensitivity is an exaggerated sunburn response. Patients typically present with skin erythema in the absence of a history of excess sun exposure; severe cases develop blistering with subsequent desquamation (shedding of epidermal scaling). Occasionally signs resembling porphyria, such as skin fragility and vesicles may be present as well as eczematous or lichenoid features. In a few cases alteration of skin or nail discolouration without previous inflammation can also be observed. It is sometimes hard for doctors to differentiate between sunburn and a mild drug-induced photosensitivity response.

The diagnosis of drug-induced photosensitivity is usually straightforward, as long as the possibility of such an eruption has been considered. Thus, a precise drug history must be taken in all patients presenting with cutaneous photosensitivity. Minimal erythema dose (MED) testing to UVA (and UVB and visible light) may be used to confirm the diagnosis if the patient is still on the potential photosensitizing drug. Lower MED values are detected in patients suffering from drug-induced photosensitivity while they are on the drug compared to when the medication is stopped. The majority of photosensitizing drugs have an action spectrum within the UVA range. If available, monochromator testing or photo-patch test with the suspected chemical can be of benefit in confirming the diagnosis.

The treatment of drug-induced photosensitivity may require discontinuation of the triggering pharmaceutical agent. The acute photosensitivity reaction is usually self-limiting. Symptomatic treatment with topical systemic steroids is sometimes indicated. Education of patients prescribed known photosensitizing drugs should include sun avoidance advice combined with recommendations concerning photoprotection with clothing and sunscreens. Thus, photosensitizing medication which may be important for the patients' health may be used if necessary.⁵³ In some patients with drug-induced photosensitivity, dose reduction may be all that is required.

Smith-Lemli-Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is a rare congenital multiple malformation syndrome first described in 1964.⁵⁴ Mutations in the dehydrocholesterol reductase gene (DHCR7), inherited as an autosomal recessive trait, result in a deficiency in 7-dehydrocholesterol reductase; this results in minimal de novocholesterol synthesis. Mental retardation is characteristic and associated with one or more of the following features: failure to thrive, dysmorphic facies, cleft palate, congenital heart disease, hypospadias and toe syndactyly. More than half of patients with SLOS have severe photosensitivity to UVA which commences in infancy.^55–57 The latent period between sun-exposure and onset of this photosensitivity reaction is typically less than 30 min. This photosensitivity eruption is characterised by confluent erythema without papules or scaling; it typically lasts for 24–48 h.^55–57 Sun avoidance may be difficult due to the child's behavioural difficulties. Management of photosensitivity in SLOS is by sun-avoidance, clothing and use of sunscreens formulated to provide a high level of protection against UVB and UVA.

The precise mechanism of the photosensitivity is not yet understood, but is not explained by the presence of higher levels of 7-DHC, the substrate of dehydrocholesterol reductase, as it does not absorb at UVA wavelengths. However, a metabolite of 7-DHC, 9-DDHC which does absorb strongly in the UVA range has been detected in the plasma of SLOS patients⁵⁸ and in the skin of mouse models of SLOS. This group discovered the presence of reactive oxygen species in UVA-exposed cells containing 9-DDHC and suggested that the generation of these may play a role in the photosensitivity experienced by some patients with SLOS. Cells kept in the dark were not damaged by 9-DDHC.⁵⁸ Another possible mechanism is via photoinduced allergens consistent with the increased susceptibility to allergy seen in these patients. Altered cholesterol metabolism alters the lipid rafts in mast cell membranes increasing their responsiveness to IgE receptor stimulation, causing hyperdegranulation.⁵⁹

Polymorphic light eruption

Polymorphic light eruption is a very common, acquired, immune-mediated photosensitivity syndrome. The typical clinical features of PLE are itchy papulo-vesicular lesions involving sun-exposed skin. The condition is typically confined to spring and summer with symptoms developing in a cyclical fashion. Skin lesions most commonly occur several hours to a few days after sun exposure. The duration of the eruption varies between 1–14 days. The rash tends to resolve spontaneously without scarring in autumn. Repeated UV exposure, either narrow-band UVB or natural sunlight, may induce the skin to become tolerant to sunlight.

The estimated lifetime prevalence of PLE was found to be 18% in a recent multicentre European study; more females are affected then males (3 : 1 ratio). The onset of the disease is typically in young adulthood, around the 2nd to 3rd decade of life. A mechanism involving the generation of a UV-induced antigen has been suggested⁶⁰ with a delay in appearance of the lesions consistent with a type IV delayed-type hypersensitivity.⁶⁰ Recent research has tested the hypothesis that failure of normal UV-induced immunosuppressive effects is responsible for the immunological reaction.^61–64 There is evidence that migration of Langerhans cells away from the skin in response to UV occurs at a reduced rate in PLE patients and that this may be responsible for an increased sensitisation to UV-induced antigens^63,64

A family history of PLE is very common and has prompted several genetic studies that suggest a dominant inheritance.^65–67 In addition, a positive family history of PLE is frequently observed in AP suggesting a potential common genetic background.⁶⁶

The diagnosis of PLE is usually easy being based on the characteristic history and clinical features. Additional tests are seldom required to confirm the diagnosis. In cases of diagnostic uncertainty, lupus serology and a porphyrin screen may help by excluding other photosensitivity disorders. The diagnosis may be supported, especially in atypical cases, by histology and skin photo testing. Monochromator light testing is generally negative but photo-provocation testing with broad-band UVA is often positive. The disease triggering action spectrum is usually in the UVA rather than the UVB range.

The management of PLE requires a diagnosis, a detailed explanation to the patient and a clear and concise information sheet for the patient. Photoprotection advice should include the use of appropriate clothing, sun avoidance and regular application of broad-spectrum sunscreens;⁶⁸ this is usually sufficient for the majority of PLE patients. Although no study has analyzed the efficacy of potent topical corticosteroids in PLE it is generally accepted that they help to clear mild to moderate attacks in many patients. Second line treatment for PLE includes systemic steroids given for a few days to settle more severe episodes.⁶⁹ More problematic cases may require annual desensitisation treatment by phototherapy (narrow-band UVB or PUVA) most frequently administered in early spring.⁷⁰ When starting the latter treatment it is important to note that PLE may be triggered while undergoing phototherapy. Severe or resistant cases of PLE may require more potent therapy; options include hydroxychloroquine,⁷¹azathioprine⁷² and cyclosporine.⁷³

Phytophotodermatitis

Phytophotodermatitis is a non-immunologic, phototoxic cutaneous reaction induced by the activation of photosensitizing plant derivates via sunlight. Numerous plants such as celery, lime, figs⁷⁴ or grasses like giant hogweed⁷⁵ contain natural sun-sensitizing substances called furocoumarins, which can be excited by long wavelength UVA triggering phytophotodermatitis. The condition can be a form of occupational dermatitis affecting people with certain professions such as groundsmen,⁷⁶ florists, chefs or gardeners. Parsnip picking as a seasonal work has also been reported to provoke phytophotodermatitis.⁷⁷

Symptoms typically appear a few hours following contact with photosensitizing plants and subsequent sun exposure. Presenting lesions are usually pruritic, erythematous, sometimes bizarre shaped patches or plaques but blistering⁷⁸ is also a fairly common manifestation. After healing, post-inflammatory hyperpigmentation⁷⁹ or photosensitivity of the formerly affected skin may persist for months.

If suspicion of this diagnosis arises, a careful history focusing particularly on work-related and recreational plant exposure often results in the obvious diagnosis of phytophotodermatitis. Occasionally the condition can be mistaken for other diseases such as allergic contact dermatitis, severe sunburn, chemical burn, infectious skin diseases or even child abuse.⁸⁰ Physical examination of the skin reveals areas of sparing at sites covered with clothing at the time of plant and sun exposure. Diagnostic tests are generally not needed to confirm the diagnosis.

No specific treatment is available for the condition. Further damage can be prevented by washing off the photo-sensitizing plant material from the skin. Sun protection is important especially in case of residual photosensitivity. In order to avoid future exposure patient education is crucial. An example of attempts at prevention of phytophotodermatitis at a population level are the warning signs adjacent to giant hogweed growing profusely on riverbanks. In patients with mild symptoms, wet dressings, local wound care and topical corticosteroids can be used successfully. More severe cases require systemic antihistamines with oral corticosteroids to decrease the signs and symptoms of this condition. Very severe examples of phytophotodermatitis may need potent analgesics, surgical debridement and skin grafting.⁸¹

Lupus erythematosus

Lupus erythematosus (LE) is a chronic, autoimmune, multifactorial, and polygenic disease. Cutaneous features, summarized as cutaneous lupus erythematosus (CLE), are present in approximately 70–75% of systemic lupus erythematosus (SLE) patients throughout the course of their disease. SLE a rare condition that is about ten times more frequent in females than in males. Subacute cutaneous lupus (SCLE) also affects women more than men. The male-to-female ratio for discoid lupus erythematosus (DLE) is about 1 : 2. DLE is slightly more frequent in blacks than in other racial groups. Skin lesions in lupus are characterized as non-specific or specific manifestations according to current classification based on Gilliam's observations in 1977. Vascular lesions such as periungual teleangiectasia, Raynaud's phenomenon, thrombophlebitis and various forms of cutaneous vasculitis are all non-specific features. Other non-specific features include alopecia, calcinosis cutis, bullous lesions and erythema multiforme. Specific clinical patterns of disease are further divided into four subgroups: acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE) and intermittent cutaneous lupus erythematosus (ICLE).

Photosensitivity is a common and well-known phenomenon in LE impairing the quality of life of affected individuals.⁸² UV radiation can induce and aggravate skin lesions in LE patients. Both UVB and UVA irradiation are capable of triggering and reproducing cutaneous lesions in LE patients under experimental circumstances.⁸³ The latent period for evolution of cutaneous lesions after UVR varies from a few days to two weeks or more; UV-exacerbated LE may persist for months.⁸⁴ The foundation of photosensitivity remains to be fully characterized, although various mechanisms are recognized. Modulation of antibody location (from the nucleus to the cell surface), UV-mediated induction of apoptosis with autoantigens in apoptotic blebs, cytotoxic effects, up-regulation of adhesion molecules, cytokines and chemokines, UV-generated antigenic DNA and expression of inducible nitric oxide synthase have all been implicated.^84,85

Cutaneous LE lesions are often localised to sun-exposed sites. ACLE presents most commonly as an erythematous rash on the cheeks in a “butterfly” distribution; however, the rash is often more generalized. SCLE lesions are generally either papulosquamous (psoriasiform) or annular, predominantly localized on the anterior chest, upper back, shoulders and neck. The most common variant of CCLE is discoid lupus erythematosus (DLE) with thick, scaly, well-demarcated plaques on the face, scalp and ears. These lesions have a tendency to scar resulting in skin atrophy and pigmentary changes. Other variants of CCLE include hyperkeratotic lupus, lupus profundus and chilblain lupus; lupus erythematosus tumidus (LET) represents the intermittent variant of cutaneous lupus, ICLE. Lupus tumidus is the most photosensitive subset of LE, followed by SCLE; DLE patients are somewhat less photosensitive.⁸⁴ Cutaneous LE lesions are unsightly and disfiguring producing a large impact on quality of life. Fortunately, CLE is otherwise asymptomatic but occasionally mild itching may occur.

Physical examination confirming features of cutaneous lupus in patients with a history of light sensitivity raises the possibility of a diagnosis of LE. Confirmation of the diagnosis requires various other tests. Serologic studies may reveal the presence of autoantibodies such as anti-Ro, anti-La, antinuclear, anti-double strand-DNA antibodies. These antibody changes are most commonly present in SLE, followed by SCLE and are least typical for DLE. Histological examination can include direct immunofluorescence to identify immunoglobulin and/or complement deposition at the dermo-epidermal junction; this is positive in about 90% of lesional biopsies of DLE patients. The lupus band test (immunoreactants in the basement membrane zone) is generally positive in SLE patients, although it is neither specific nor sensitive. Common histopathological features in LE are vacuolar degeneration of the basal cells, thickening of the basement membrane, epidermal atrophy and inflammatory – usually lymphocytic – infiltrate in the dermis. Phototesting with UVB, UVA and visible light is helpful in many cases especially photoprovocation followed by the appearance of typical lesions. Minimal erythema dose values are sometimes lower in LE patients compared to controls.⁸⁶

A number of topical and systemic treatments have been tried in patients with cutaneous LE with mixed results.^87,88 Topical corticosteroids or calcineurin inhibitors are frequently used as they are safe and convenient. Severe cases of cutaneous lupus may require systemic therapy; anti-malarial drugs represent the first-line systemic treatment (usually hydroxychloroquine). Alternative options include dapsone (particularly useful for bullous cases), methotrexate, oral retinoids (especially for hyperkeratotic lesions), thalidomide (sometimes used in chronic, refractory DLE), azathioprine, mycofenolate mofetil and systemic steroids. In selected cases, new immunomodulatory biological agents such as rituximab, anti-TNFα biological therapies and efalizumab have also been used. Laser treatment has been reported to be of benefit for the vascular lesions of cutaneous lupus. UVB hardening therapy has also been administered to some patients with good results.⁸⁹ Several studies showed that UVA1 irradiation can reduce disease activity in some patients suffering from SLE.^90,91Photoprotection is crucial in light sensitive LE patients to prevent exacerbation and aggravation of symptoms.⁹²

UVA protection

The common factor in the management of all of the skin conditions described in this paper is the need for photoprotection. UVA is generally more difficult to protect against than UVB; the longer wavelengths penetrate skin more easily than UVB. Additionally, UVA can penetrate through a greater variety of materials, including some car windows. Many sunscreens provide good protection against UVA; however, there is a lack of availability of UVA-specific sunscreens. Furthermore, there is no clear definition of what constitutes an adequate degree of UVA protection.

The Lancet published a review in 2007 examining all aspects of sun protection.⁹³ The authors remind us that the average cotton t-shirt gives equivalent to only SPF 10 protection and the commercially available UV protective clothing items often little more than this. Both organic and inorganic sun creams are widely available. The latter (titanium oxide and zinc oxide) form a physical barrier of inorganic particles over the skin which absorbs and reflects ultraviolet radiation. They are often cosmetically less acceptable than their organic counterparts; micronisation (reducing particle size) has been used to improve this factor. Zinc oxide is more effective in UVA protection. Organic sunscreens act by absorbing radiation, and those developed for the UVA spectrum have only relatively recently been introduced. Tinosorb M has good action in the UVA range and Mexoryl XL covers both UVB and UVA.

Sunscreens should not be used in order to increase potential sun exposure. Ideally, sunscreens should be applied liberally and frequently. The recommendation from dermatologists is that patients should use sunscreens that provide adequate UVA protection; the definition of this remains unclear. In August 2007 the FDA advising a UVA protection rating of one to four stars (low, medium, high, highest) based on in vivo and in vitro assays. Developing concepts for specific UVA protection include bacterially produced melanin which has shown some photoprotection against UVA wavelengths and has been suggested as a potentially viable sunscreen for those with photosensitivity.⁹⁴

Conclusion

The UVA-mediated photosensitivity disorders include a diverse range of conditions some of which are rare or very rare. However, drug-induced photosensitivity is not uncommon and is usually mediated by UVA; polymorphic light eruption is a very common disorder. Clinical research has helped to advance our understanding of all of the conditions included in this review. There are grounds to be optimistic that further progress will be made in the coming decade, and that new treatments will help to reduce the impact on patients of these distressing UVA-mediated disorders.

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Footnotes

† Contribution to the themed issue on the biology of UVA.

‡ RMP is currently a freelance lecturer and science writer based in Cardiff.

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