Chronic actinic dermatitis

 

Salient features

 

·        Chronic actinic dermatitis is a rare, acquired, persistent eczematous eruption (acute, subacute or chronic lichenified) of exposed skin, sometimes having pseudolymphomatous (reticuloid) features.

·        It commonly affects older men over 50 years of age but is increasingly recognized in women and in younger people, including children.

·        Histologic features are eczematous, but pseudolymphomatous forms may be virtually indistinguishable from cutaneous T-cell lymphoma.

·        It usually involves severe ultraviolet B sensitivity but often also involves ultraviolet A sensitivity and sometimes sensitivity to visible light.  Positive patch or photo patch tests common.see

·        Persistent light reaction, actinic reticuloid, photosensitive eczema, and photosensitivity dermatitis are all considered either clinical variants or old diagnostic terms.

·        It is likely the result of a delayed-type hypersensitivity reaction against an endogenous photo induced epidermal antigen(s).

·        Therapy consists of strict avoidance of the relevant ultraviolet and visible rays, avoidance of (photo) contact sensitizers, along with topical and intermittent oral steroids, and topical calcineurin inhibitors. Occasionally, low dose psoralen-ultraviolet A photo chemotherapy can be used, guided by the findings of investigation, particularly photo testing. If these measures are insufficient, or cause too much disruption to quality of life, then systemic immunosuppression (such as azathioprine, cyclosporine or methotrexate) is required.

 

Introduction

Chronic actinic dermatitis (CAD) is an uncommon, persistent or recurring eczematous eruption predominantly affecting photo‐exposed skin, sometimes having pseudolymphomatous features, in association with abnormal photosensitivity. The photosensitivity is usually to broad‐band, predominantly UVB, wavelengths.

Age

Commonly affects elderly males above the age of 50 years, especially outdoor workers. CAD is the second most commonly diagnosed idiopathic (immunological) photodermatosis after PLE.

Associated diseases

Chronic actinic dermatitis is associated with contact and/or photo contact allergy in most patients. CAD associated with atopic eczema is commonly found in young patients. Rarely CAD is associated with human immunodeficiency virus infection.

 

 

Etiology and Pathogenesis

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The action spectra for CAD include: UVB; UVB and UVA; UVB, UVA and visible light; and, rarely, UVA alone, with UVB plus UVA being the most common. +CAD probably represents a contact allergy-like delayed-type hypersensitivity reaction against an endogenous photo induced epidermal neo antigen(s). In addition to hypersensitivity to cutaneous photo neo antigens, patients with CAD often have concomitant allergic or photo allergic contact dermatitis to airborne or other ubiquitous allergens, including plant compounds, fragrances, and medicaments. Commonly implicated allergens include sesquiterpene lactone from plants of the Compositae family and sunscreens. A recent study indicates that sesquiterpene lactone remains the most common allergen in patients with CAD, with positive and clinically relevant photo patch testing to this allergen documented in approximately 20% of patients. It is therefore possible that in CAD chronic photo damage leads to a partial abrogation of normal cutaneous immunosuppression, thereby permitting enhanced cutaneous immune responsiveness against an otherwise weak endogenous photo antigen.

 

When CAD occurs in the absence of an obvious epicutaneous contact allergen, the relevant novel antigen must be either directly radiation-induced or formed indirectly as a result of secondary oxidative metabolism. Important support for the latter possibility comes from the fact that albumin can become antigenic in vitro through photo oxidation of its histidine moieties. There is no evidence for a genetic susceptibility to CAD; however, one stimulus for the acquisition of skin reactivity may be concurrent allergic contact dermatitis to recognized exogenous sensitizers or photosensitizers, often airborne, which may predispose by altering cutaneous immunity, and thus permitting immunological recognition of an endogenous photo antigen. Long-standing endogenous eczema, drug-induced photosensitivity, human immunodeficiency virus infection, and possibly PLE may also play similar roles. On the other hand, in addition or instead, chronic photo damage in frequently sun-exposed elderly outdoor enthusiasts, those who most often develop CAD, may impair normal UVR-induced skin immunosuppression sufficiently for endogenous UVR-induced photo antigens to be recognized, as apparently also occurs for genetic reasons in PMLE.

In summary, CAD appears to be an allergic contact dermatitis-like reaction against UVR-altered DNA or similar or associated molecules, perhaps as a result of enhanced immune reactivity due to concomitant airborne contact dermatitis or a reduced immunosuppressive capacity in photo damaged skin. The eruption occurs most often in patients with long-standing exposure to sunlight and airborne contact allergies.

 

 

It is uncommon to develop CAD in the absence of a pre‐existing dermatitis. There may also be a lengthy prodrome of dermatitis such as allergic or atopic eczema, before photosensitivity develops. The concept is that an underlying chronic dermatitis becomes secondarily photosensitive and then light alone is sufficient to keep the disease active. As the condition is now independent of the original photo allergen and is aggravated by each new solar exposure, avoidance of photo allergen does not cure the disease.

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Pathology

 

The histology of CAD is not specific. There is epidermal spongiosis and acanthosis, lymphocytic exocytosis, and a perivascular lymphocytic cellular infiltrate confined to the upper dermisthat in milder cases may resemble chronic eczema. Severe CAD, in pseudolymphomatous forms however, may mimic cutaneous T-cell lymphoma (CTCL), on occasion being virtually indistinguishable.

 

 

 

Clinical features

 

Relatively sun-protected sites include the upper eyelids, the nasolabial folds, the retroauricular areas, the submental region and the deepest portion of skin furrows. In airborne contact dermatitis these areas may be involved.

 

 

History

 

+CAD may develop de novo in apparently normal skin or in the skin of patients with previous endogenous eczema (often atopic or seborrhoeic eczema), in patients with a prior history of dermatitis (in particular, photo allergic or allergic contact dermatitis), or rarely following longstanding oral drug photosensitivity or PLE. Coexistent allergic contact sensitivity to plant allergens, fragrances, or sunscreens is common.  The condition usually affects middle-aged or elderly men; however, CAD is increasingly recognised in younger people, particularly in those with atopic eczema, although it is rarely present in children. The disorder is worse in summer, developing within minutes to hours after sunlight exposure and producing a pruritic confluent erythematous eruption that occasionally remits over several days with scaling, if exposure ceases and if the reaction is mild. However, severely affected patients frequently do not even recognize that exacerbations are related to sunlight exposure, especially when affected all year round and when the wavelengths of sensitivity extend to longer UVA or visible wavelengths not associated with normal sunburn.

 

Cutaneous lesions

 

+++Presentation can be diverse and features may also vary within the same patient. For example, with persistent, uninterrupted inflammation, pseudo‐lymphomatous areas can develop; these may be the only sites of activity seen in winter, whereas in summer the lesions are eczematous, patchy or confluent, which may be acute, subacute or chronic in nature. Acutely, there may be an erythematous, exudative, vesicular dermatitis on photo‐exposed sites; in chronic cases there is lichenification. The skin is thickened, furrowed and often covered with scale. In some cases leonine facies evolves. Less commonly, scattered or widespread, erythematous, shiny, pseudo-lymphomatous infiltrative papules or plaques may be present on a background of erythematous, eczematous, or normal skin in severely affected individuals. In patients of higher skin ­phototype (IV to VI) there can be nodular prurigo‐like morphology.

 

Habitually exposed sites are predominantly affected, particularly the face, bald scalp, back and sides of the neck, upper chest and dorsal aspects of the forearms and hands with  sharp cut-off at lines of clothing, and often with sparing in the depths of skin furrows, upper eyelids, creases under the eyes and in  areas under the lower lip, submental region, finger webs, nasolabial folds and post auricular areas (Wilkinson's triangle should be examined by pulling the ear forward). In severe disease, eczema of palms and soles may also be found. Eyebrows, eyelashes and scalp hair may be stubbly or altogether lost from constant rubbing and scratching. There is frequent involvement of covered areas and erythroderma rarely develops in severely affected patients. The patients are so sensitive to light that minimum amount of energy passing through their clothing may be enough to trigger a reaction.

 

Variable, sometimes geographic, sparing of exposed areas of the face or elsewhere, as well as irregular hyper pigmentation and hypo pigmentation, sometimes vitiligo-like, may also occasionally be found.

 

Diagnosis

 

This is suggested by the typical clinical findings in conjunction with normal antinuclear factor and extractable nuclear antibody titres, and normal blood, urine and stool porphyrin concentrations. The provoking wavelengths are UVB in virtually all patients, UVA also in most and visible light in addition in some.

 

In severe or erythrodermic CAD, there may be large numbers of circulating CD8⁺Sézary cells without other suggestions of malignancy. Human immunodeficiency virus status should be assessed if there is suspicion that this may be a predisposing or associated factor. Serum IgE may be elevated (even among those whose CAD has not supervened upon atopic eczema), with higher levels of IgE correlating with more severe disease.

 

 

Laboratory Tests

 

Photo testing

 

Monochromator photo testing to UV and ­visiCDble wavelengths across the solar spectrum is the investigation of choice ++.to confirm the diagnosis of CAD. Almost invariably one finds low erythemal thresholds and eczematous or pseudolymphomatous responses after irradiation with UVB, usually with UVA, and rarely with visible wavelengths. A small number of patients react only to UVA, and fewer still only to visible light, in which case, drug photosensitivity must be excluded.

 

 

Patch and Photo patch Testing

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+Patch and photo patch testing is essential when CAD is suspected. Approximately 80% of patients with CAD show positive patch and/or photo patch testing to a diverse range of common allergens such as fragrances, rubber additives, nickel, colophony, medicaments and sunscreens. Plant contact allergy in CAD is also very common, notably to Asteracea (Compositae), lichens and oleoresins.

 

 

Differential diagnosis

Airborne contact dermatitis typically involves the upper eyelids and under the nose and chin, while the back of neck is spared. Photo aggravated atopic or seborrhoeic eczema may be impossible to distinguish from CAD on clinical grounds. Likewise, drug‐induced photosensitivity and cutaneous T‐cell lymphoma, the latter especially if there is erythroderma, must be considered.

 

In photo aggravated atopic or seborrhoeic eczema, photo testing will be normal. In airborne contact allergy or in photo contact allergy, photo testing is normal but patch and/or photo patch testing are positive. In drug‐induced photosensitivity there will usually be predominant UVA sensitivity in a patient taking a photoactive drug and the morphology of the eruption is usually not eczematous.

 

In contrast to CTCL, CAD infiltrates are predominantly CD8⁺ cells and T-cell receptor gene rearrangement studies are negative. Very rarely, primary CTCL may present with severe CAD features and should therefore be considered if apparent CAD is totally refractory to treatment.

 

In erythrodermic CAD, Sezary syndrome/T‐cell lymphoma needs to be excluded and photo testing in the latter, if feasible, is usually normal. Occasionally, a few atypical circulating cells can occur in erythrodermic CAD. If in doubt, T‐cell receptor gene rearrangement studies can be undertaken to confirm the polyclonal nature of CAD.

 

Erythrodermic CAD must be differentiated from other causes of erythroderma, but histologic features may not allow discrimination so photo testing after the erythroderma has been controlled can assist in establishing the diagnosis.

 

 

Course and prognosis

 

Once established, CAD usually persists for years before resolving gradually. The dermatitis is so light-sensitive and pruritic that it is impossible for them to lead a normal life. They frequently express suicidal thoughts. Particularly severe photo test sensitivity and a number of completely separate contact allergens seem to be predictors of a poorer prognosis for resolution. In addition, female sex and young age are also associated with poorer prognosis for resolution.

 

 

Treatment

 

Establishing the diagnosis, excluding drug photosensitivity and defining the action spectrum for abnormal photosensitivity are all paramount. If a patient is taking a photoactive drug such as thiazide or quinine, this should be stopped and repeat phototesting undertaken 3–6 months later. Treatment involves the prevention of flares and the suppression of active disease.

Strict photo protection by careful avoidance of UVR, and when necessary visible light, by using behavioural modification, hats, clothing , education and high‐factor, broad‐spectrum, non‐fragranced, low‐allergenic sunscreens are fundamentally important. For patients who are UVA sensitive, UV‐absorbing window film can be helpful. Exacerbating contact allergens and photo allergens must be identified and avoided indefinitely. Patients should also be aware of the need to optimize dietary vitamin D intake and if necessary to take supplements. Repeat phototesting at intervals, and if indicated patch/photopatch testing, should be considered in order to ascertain if there are changes in photosensitivity and to identify new allergens.

First line

The treatment of established disease involves the use of topical corticosteroids. Strong topical steroids such as clobetasol propionate are often needed and frequently produce marked symptomatic relief without adverse effects, even after long-term use, if confined to affected skin.

Second line

In more resistant disease, the topical calcineurin inhibitors—tacrolimus and pimecrolimus—sometimes produce good results if tolerated. If topical measures are inadequate, oral glucocorticoids may be used in acute flares. For refractory disease PUVA is the treatment of choice and includes long-term very low-dose PUVA, usually several times weekly initially followed by maintenance exposures about every 3 weeks may be helpful, generally accompanied by oral and topical corticosteroid cover in the early stages to prevent disease flares. Ordinary phototherapy with UVA and /or UVB should be avoided. It only worsens the condition.

Third line

If PUVA fails, oral immunosuppressive therapy is almost always necessary and generally helpful if tolerated. Azathioprine has proven to be the most effective treatment, often in very low doses such as 50 mg daily. It can be discontinued in winter months once control is achieved and may be required annually during periods of increased sun intensity. Cyclosporine 3.5 to 5.0 mg/kg/day can be rapidly effective, but is more likely to produce adverse effects, and so is generally not a good long term treatment. Methotrexate is also used, especially when CAD has arisen on a background of atopic eczema. Mycophenolate mofetil (1-2gm/day) is less often useful.

 

With careful management about 1 in 10 patients will lose their photosensitivity within 5 years, 1 in 5 by 10 years, and half of patients by 15 years.

 

 

Prevention

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The risk of CAD can probably be reduced by moderating outdoor pursuits, especially those associated with plant allergen exposure such as gardening, even more so for individuals who already have a tendency to develop eczematous eruptions in exposed areas. In those persons who are already developing CAD, avoidance of UVR is critical, and patients should be aware that indoor lighting with fluorescent lamps, including compact fluorescent energy-saving lamps, is also a source of UVA and UVB. Watching television, using computers and artificial lighting exposure are not a problem for most patients.