C h ron i c A c t i n i c Dermatitis So Yeon Paek, MD*, Henry W. Lim, MD KEYWORDS Chronic actinic dermatitis Actinic reticuloid Photosensitive eczema Photosensitivity dermatitis Persistent light reaction Photodermatosis
KEY POINTS
HISTORY
EPIDEMIOLOGY
Chronic actinic dermatitis (CAD), previously known as actinic reticuloid, photosensitivity dermatitis, photosensitive eczema, and persistent light reaction, is an immunologically mediated photodermatosis characterized by pruritic eczematous lesions of areas exposed to the sun.1–5 Haxthausen6 first described this condition in 1933 in a patient with hypersensitivity to light after intravenous trypaflavine, a photosensitizing dye. Actinic reticuloid and two milder forms of CAD, referred to as photosensitive eczema and photosensitivity dermatitis, were reported in 1969.7,8 By 1979, Hawk and Magnus9 had introduced the term “chronic actinic dermatitis,” but it was not until 1990, when Lim and colleagues10 suggested unifying the variants under the same name, that the term became widely accepted.11
CAD has been reported in the United States, Europe, Asia, and Africa, with increased incidence in the summertime when sun exposure is greatest.12–16 It commonly affects men older than 50 years who work or enjoy the outdoors. This condition can affect individuals of all skin types, although in the United States it is more commonly reported in persons with Fitzpatrick skin types V and VI.17–20 In patients seen in the United Kingdom, but not those examined in the United States or Japan, CAD can be associated with contact allergy or photocontact allergy to Compositae oleoresins, a group of airborne plant allergens, presumably caused by exposure through gardening.21–24 There is no familial inheritance. Association with human immunodeficiency virus (HIV) infection has been reported; as a group,
Disclosure Statement: No conflicts of interest. Department of Dermatology, Henry Ford Hospital, 3031 West Grand Boulevard, Suite 800, Detroit, MI 48202, USA * Corresponding author. E-mail address: [email protected] Dermatol Clin 32 (2014) 355–361 http://dx.doi.org/10.1016/j.det.2014.03.007 0733-8635/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
derm.theclinics.com
Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis characterized by pruritic eczematous lesions of sun-exposed areas. Evaluation should include histologic examination, phototesting, and laboratory workup, including human immunodeficiency virus (HIV) test and Sezary count. The most common action spectrum is ultraviolet B (UVB) plus ultraviolet A (UVA), although CAD may also be seen with UVB or UVA alone, or with a combination of UVB, UVA, and visible light. Management begins with strict photoprotection, topical corticosteroids, and topical calcineurin inhibitors. Other treatments with noted efficacy include oral prednisone, cyclosporine, azathioprine, and mycophenolate mofetil. Proper diagnosis and management are essential, as CAD can have a moderate to large impact on quality of life.
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Paek & Lim these patients tend to be younger than CAD patients without HIV infection.25
PATHOGENESIS The pathogenesis of CAD has not been completely elucidated. The clinical and histologic features, the presence of mostly CD81 T cells in the dermis, and the pattern of adhesion molecule activation in CAD resemble allergic contact dermatitis.26 Thus, a mechanism of delayed-type hypersensitivity can be inferred. However, rather than an exogenous agent, the cutaneous antigen is likely endogenous and photoinduced. Though not proven, it is possible that a pathophysiology similar to that described in polymorphous light eruption (PMLE) also occurs in CAD.27 In normal healthy individuals, exposure to sunlight results in localized immunosuppression; therefore, there are no obvious clinical lesions even in the presence of photoinduced neoantigens in the skin. However, similarly to PMLE, it is possible that patients with CAD are less likely to be photoimmunosuppressed, resulting in a brisk response to the presence of ultraviolet (UV)-induced neoantigens in the skin, which manifest as cutaneous lesions. The antigenic molecule in CAD has been theorized to be DNA, which absorbs UV radiation and is the molecule thought to be involved in sunburn.27,28 The action spectrum for CAD is similar to that for sunburn, but at lower doses.29
DIAGNOSIS Clinical Manifestations Skin findings of CAD include eczematous and often lichenified pruritic patches and confluent plaques limited to sun-exposed areas of the scalp, face, neck, chest, arms, hands, and back, with
notable sparing of sun-protected areas, such as nasolabial folds, submental chin, upper eyelids, retroauricular areas, skin creases, and finger web spaces (Fig. 1). Acute flares are associated with erythematous patches and papules with fine scale on sun-exposed areas (Fig. 2). In severe cases, papules and plaques may occur on sunprotected sites, albeit to a lesser extent than on sun-exposed areas; rarely, erythroderma and hyperkeratosis of palms and soles may be observed (Fig. 3).30
Differential Diagnoses Conditions that may mimic CAD include drug eruption, allergic or photoallergic contact dermatitis, cutaneous T-cell lymphoma (CTCL),31 and connective tissue diseases (such as acute or subacute cutaneous lupus erythematosus). Careful history taking, examination of morphology and distribution of lesions, and appropriate photobiological and laboratory investigations are essential in arriving at the correct diagnosis (Table 1).32
Histology Pathologic examination of CAD demonstrates spongiotic dermatitis with lymphohistiocytic infiltrate and variable acanthosis. Atypical lymphocytes and exocytosis seen in some specimens may mimic histologic changes of CTCL. Papillary dermal fibrosis and a brisk infiltrate, both histologic signs of chronicity, may also be found. In severe cases the biopsy may show focal epidermal necrosis, papillary dermal collagen, fibrin deposition in the dermal-epidermal junction, and erosions.
Photobiological Evaluation Phototesting is recommended for further evaluation of suspected CAD. If a monochromator or
Fig. 1. Clinical features of chronic actinic dermatitis (CAD). (A) Erythema, lichenification, and scale on sunexposed skin. Note sparing of postauricular area. (B) Lichenification of sun-exposed sites, with sharp cutoff of sun-protected areas of the skin.
Chronic Actinic Dermatitis which are set to replace common incandescent lamps in Europe, may be a potential harmful source of UV radiation with prolonged exposure in patients with photosensitive conditions. These lamps contain mercury, which activates the phosphor-coated walls, emitting UV radiation in the UVB and UVA range. Patch testing and photopatch testing may also be considered if warranted by the history of the patient. Patients with CAD in the United Kingdom often demonstrate positive patch testing to relevant Compositae, presumably resulting from exposure from gardening.
Fig. 2. Acute flare 24 hours after inadvertent sun exposure in a patient with CAD. Note diffuse erythema on the face and superficial erosions on the nose.
solar simulator is unavailable, testing with ultraviolet A (UVA; 320–400 nm) or ultraviolet B (UVB; 290– 320 nm) therapy units and a slide projector (to test visible light) may be considered.33 The most common action spectrum for CAD is UVB plus UVA, resulting in a decreased minimal erythema dose (MED) for both UVB and UVA in most patients.29,34 However, CAD may be seen with decreased MEDB or MED-A alone (12%–25%), or with a combination of sensitivity to UVB, UVA, and visible light. A study conducted by Eadie and colleagues35 also found that compact fluorescent lamps (CFLs),
Fig. 3. Hyperkeratosis and scale on palms of a patient with CAD.
Laboratory Evaluation Lupus serologies, such as antinuclear antibody (ANA) and anti-Ro/anti-La antibodies, may be obtained and should be negative. Sezary-like cells may be seen in erythrodermic CAD, but the CD4:CD8 ratio will be low and T-cell clonality will be absent.36 In addition, testing for HIV is recommended, especially in younger patients, in whom CAD may be a presenting sign of HIV.25
MANAGEMENT Strict photoprotection is key in the management of CAD.37 Patients should be advised to wear broadspectrum (UVA and UVB) sunscreen with a minimum sun-protection factor of 30, long-sleeved clothing, and wide-brimmed hats, and to seek shade during peak hours (between 10 AM and 4 PM). Clear museum films or UVA filters may be applied to windows to block most UV transmission.38 It should be noted that there is no evidence that television and computer screens might exacerbate this condition. In addition to photoprotection, patients may use topical corticosteroids or topical calcineurin inhibitors as first-line therapy. Mid-potency to highpotency topical corticosteroids are effective for the control of disease flare. However, the potential risks of skin atrophy, striae, and dyspigmentation preclude their long-term use. Many case reports and case series support the therapeutic benefit of topical tacrolimus 0.1% ointment, daily to twice daily, for CAD.39–46 Tacrolimus (Protopic) binds to FK506-binding protein, blocking dephosphorylation of nuclear factor of activated T cells, and preventing transcription of interleukin-2 and other inflammatory cytokines. In CAD, this seems to work by inhibiting T-lymphocyte activation by suppressing Langerhans cells.47 Similar results have been achieved with topical pimecrolimus (Elidel) cream for CAD.48 Patients must be informed of the black-box warning for increased risk of cutaneous malignancy and lymphoma with topical
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Table 1 Evaluation of chronic actinic dermatitis Test Histology
Results in CAD
Comments
Punch biopsy
Epidermal spongiosis with May be confused with CTCL. moderately dense superficial Immunohistochemistry and Tand deep lymphocytic infiltrate cell rearrangement warranted Phototesting UVA (320–400 nm) Decreased MED Most common action spectrum for CAD is UVB 1 UVA. May also UVB (290–320 nm) Decreased MED be seen with UVA or UVB Visible light May show decreased MED alone, or with a combination of (400–700 nm) UVB 1 UVA 1 visible light Laboratory Lupus serologies ANA, anti-Ro/-La negative Rule out other CTD Peripheral smear Sezary-like cells may be seen in Immunohistochemistry and gene erythrodermic CAD, but rearrangement analysis can be CD4:CD8 ratio will be low and conducted to further T-cell clonality will be absent differentiate CTCL from CAD HIV Negative CAD may be a presenting sign of HIV in younger patients. Testing recommended in high risk patients Abbreviations: ANA, antinuclear antibody; CAD, chronic actinic dermatitis; CTCL, cutaneous T-cell lymphoma; CTD, connective tissue diseases; HIV, human immunodeficiency virus; MED, minimal erythema dose; UVA, ultraviolet A; UVB, ultraviolet B.
tacrolimus and pimecrolimus, although convincing evidence is lacking. Systemic immunosuppressive therapy is frequently used for widespread or refractory disease. Oral corticosteroids (prednisone 0.5– 1.0 mg/kg/d) can be given for several weeks at a time for flares. Chronic steroid use is not recommended because of its adverse side-effect profile, including, but not limited to, weight gain, high blood sugar, increased risk for infections, osteoporosis, and fractures, adrenal gland suppression, delayed wound healing, glaucoma or cataracts, and steroid psychosis. Other steroid-sparing agents with proven efficacy in the treatment of CAD include: cyclosporine (3.5–5 mg/kg/d),49,50 azathioprine (1.0–2.5 mg/kg/d),51,52 and mycophenolate mofetil (25–40 mg/kg/d or 1–2 g/d).53 Patients should be counseled on the increased risk of infection with these medications. Additional potential side effects are noted in Table 1. Only single case reports exist to support the treatment of refractory CAD with low-dose thalidomide54 and interferon-a.55
PROGNOSIS Spontaneous resolution of chronic actinic dermatitis has been reported to be 10% over 5 years, 20% over 10 years, and 50% over 15 years.33 These findings were established from a historical cohort study of CAD patients in a Scottish tertiary referral center, and may underestimate the actual
probability of remission. Patients may be counseled that their photosensitivity may eventually subside with photoprotection and avoidance of allergens.56 In addition, a few case reports have suggested the possibility of malignant transformation of pseudolymphomatous CAD or association with other malignancies.57–60 However, a chart review of 231 patients with CAD enrolled in the National Cancer Registry of the United Kingdom identified no significant increased risk of lymphoma and nonlymphoma cancers in a 20-year study period.61 In addition, DNA flow cytometry of affected skin from patients with CAD did not demonstrate DNA aneuploidy.62 Therefore, it does not appear that CAD is a premalignant condition, but patients should be aware of the increased risk of malignancy with immunosuppressant therapy.63,64
SUMMARY CAD is an immunologically mediated photodermatosis characterized by pruritic eczematous and lichenified plaques sharply demarcated to sunexposed areas with notable sparing of eyelids, skin folds, submental chin, postauricular skin, and finger web spaces. It mostly affects men older than 50 years. The condition is thought to be due to secondary photosensitization of an endogenous antigen in the skin, resulting from either crossreactivity with other contact allergens or photocontact allergens, or the lack of localized
Chronic Actinic Dermatitis
Table 2 Management of chronic actinic dermatitis Therapy
Dosage
Comments
Strict photoprotection
—
Broad-spectrum (UVA/UVB-block) sunscreen Topical tacrolimus (Protopic) ointment
Minimum SPF 30
Long-sleeved clothing, widebrimmed hats, sun avoidance during peak daylight hours (10 AM to 4 PM), UV filters or museum film for windows inorganic filters
Prednisone
0.5–1.0 mg/kg/d
Cyclosporine
3.5–5 mg/kg/d
Azathioprine
1.0–2.5 mg/kg/d
Mycophenolate mofetil (CellCept)
25–40 mg/kg/d (1–2 g/d)
0.1% daily to BID
Black-box warning: increased risk of cutaneous malignancy and lymphoma For acute flares only Potential side effects: weight gain, high blood sugar, high blood pressure, increased risk of infections, osteoporosis, and fractures, adrenal gland suppression, delayed wound healing, glaucoma or cataracts, steroid psychosis Side effects: gingival hyperplasia, hypertrichosis, headache, nausea, malaise, gout, hyperkalemia, hypomagnesemia, hypertension, nephrotoxicity, malignancy Side effects: myelosuppression, hypersensitivity syndrome, GI symptoms, infection, lymphoproliferative malignancy Side effects: GI upset, teratogenic, carcinogenic, neurologic symptoms (headache, tinnitus, weakness), increased risk of herpes zoster, risk of hepatotoxicity
Abbreviations: BID, twice daily; CAD, chronic actinic dermatitis; GI, gastrointestinal; SPF, sun-protection factor; UV, ultraviolet; UVA, ultraviolet-A; UVB, ultraviolet-B.
photoimmunosuppression in such patients. Histology shows epidermal spongiosis with moderately dense superficial and deep lymphocytic infiltrate, which may be confused with CTCL. The most common action spectrum for CAD seen with phototesting is UVB plus UVA. As appropriate, patch testing and photopatch testing should also be performed. Laboratory workup should be aimed at excluding other potential diagnoses, such as CTCL and acute or subacute cutaneous lupus erythematosus. CAD may be a presenting sign of HIV in young patients with risk factors. Table 2 outlines the therapeutic management of patients with CAD. Spontaneous resolution has been reported to be 10% over 5 years, 20% over 10 years, and 50% over 15 years. Therefore, patients should be counseled that their photosensitivity may
eventually subside with avoidance of allergens and photoprotection. In addition, CAD does not appear to be a premalignant condition, but clinicians should provide counseling on the increased risk of malignancy with immunosuppressant therapy. Finally, CAD can have a moderate to large impact on quality of life, so proper diagnosis and management is essential.65
REFERENCES 1. Hawk JL. Chronic actinic dermatitis. Photodermatol Photoimmunol Photomed 2004;20(6):312–4. 2. Gambichler T, Al-Muhammadi R, Boms S. Immunologically mediated photodermatoses: diagnosis and treatment. Am J Clin Dermatol 2009;10(3): 169–80.
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20. Kerr HA, Lim HW. Photodermatoses in African Americans: a retrospective analysis of 135 patients over a 7-year period. J Am Acad Dermatol 2007; 57(4):638–43. 21. Lim HW, Cohen D, Soter NA. Chronic actinic dermatitis: results of patch and photopatch tests with Compositae, fragrances, and pesticides. J Am Acad Dermatol 1998;38(1):108–11. 22. Russell SC, Dawe RS, Collins P, et al. The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis) occurring in seven young atopic dermatitis patients. Br J Dermatol 1998;138(3):496–501. 23. Yones SS, Palmer RA, Hextall JM, et al. Exacerbation of presumed chronic actinic dermatitis by cockpit visible light in an airline pilot with atopic eczema. Photodermatol Photoimmunol Photomed 2005;21(3):152–3. 24. Creamer D, McGregor JM, Hawk JL. Chronic actinic dermatitis occurring in young patients with atopic dermatitis. Br J Dermatol 1998;139(6):1112–3. 25. Meola T, Sanchez M, Lim HW, et al. Chronic actinic dermatitis associated with human immunodeficiency virus infection. Br J Dermatol 1997;137(3): 431–6. 26. Menage Hdu P, Sattar NK, Haskard DO, et al. A study of the kinetics and pattern of E-selectin, VCAM-1 and ICAM-1 expression in chronic actinic dermatitis. Br J Dermatol 1996;134(2):262–8. 27. van de Pas CB, Kelly DA, Seed PT, et al. Ultravioletradiation-induced erythema and suppression of contact hypersensitivity responses in patients with polymorphic light eruption. J Invest Dermatol 2004;122(2):295–9. 28. Freeman SE, Hacham H, Gange RW, et al. Wavelength dependence of pyrimidine dimer formation in DNA of human skin irradiated in situ with ultraviolet light. Proc Natl Acad Sci U S A 1989;86(14): 5605–9. 29. Menage HD, Harrison GI, Potten CS, et al. The action spectrum for induction of chronic actinic dermatitis is similar to that for sunburn inflammation. Photochem Photobiol 1995;62(6):976–9. 30. Somani VK. Chronic actinic dermatitis—a study of clinical features. Indian J Dermatol Venereol Leprol 2005;71(6):409–13. 31. Heller P, Wieczorek R, Waldo E, et al. Chronic actinic dermatitis. An immunohistochemical study of its T-cell antigenic profile, with comparison to cutaneous T-cell lymphoma. Am J Dermatopathol 1994;16(5):510–6. 32. Pacheco D, Fraga A, Travassos AR, et al. Actinic reticuloid imitating Sezary syndrome. Acta Dermatovenerol Alp Panonica Adriat 2012;21(3):55–7. 33. Dawe RS, Crombie IK, Ferguson J. The natural history of chronic actinic dermatitis. Arch Dermatol 2000;136(10):1215–20.
Chronic Actinic Dermatitis 34. Yap LM, Foley P, Crouch R, et al. Chronic actinic dermatitis: a retrospective analysis of 44 cases referred to an Australian photobiology clinic. Australas J Dermatol 2003;44(4):256–62. 35. Eadie E, Ferguson J, Moseley H. A preliminary investigation into the effect of exposure of photosensitive individuals to light from compact fluorescent lamps. Br J Dermatol 2009;160(3):659–64. 36. Bakels V, van Oostveen JW, Preesman AH, et al. Differentiation between actinic reticuloid and cutaneous T cell lymphoma by T cell receptor gamma gene rearrangement analysis and immunophenotyping. J Clin Pathol 1998;51(2):154–8. 37. Ferguson J. Diagnosis and treatment of the common idiopathic photodermatoses. Australas J Dermatol 2003;44(2):90–6. 38. Dawe R, Russell S, Ferguson J. Borrowing from museums and industry: two photoprotective devices. Br J Dermatol 1996;135(6):1016–7. 39. Uetsu N, Okamoto H, Fujii K, et al. Treatment of chronic actinic dermatitis with tacrolimus ointment. J Am Acad Dermatol 2002;47(6):881–4. 40. Grone D, Kunz M, Zimmermann R, et al. Successful treatment of nodular actinic reticuloid with tacrolimus ointment. Dermatology 2006;212(4):377–80. 41. Baldo A, Prizio E, Mansueto G, et al. A case of chronic actinic dermatitis treated with topical tacrolimus. J Dermatolog Treat 2005;16(4):245–8. 42. Schuster C, Zepter K, Kempf W, et al. Successful treatment of recalcitrant chronic actinic dermatitis with tacrolimus. Dermatology 2004;209(4):325–8. 43. Evans AV, Palmer RA, Hawk JL. Erythrodermic chronic actinic dermatitis responding only to topical tacrolimus. Photodermatol Photoimmunol Photomed 2004;20(1):59–61. 44. Suga Y, Hashimoto Y, Matsuba S, et al. Topical tacrolimus for chronic actinic dermatitis. J Am Acad Dermatol 2002;46(2):321–3. 45. Ogawa Y, Adachi A, Tomita Y. The successful use of topical tacrolimus treatment for a chronic actinic dermatitis patient with complications of idiopathic leukopenia. J Dermatol 2003;30(11):805–9. 46. Busaracome P, Wattanakrai P, Rajatanavin N. Chronic actinic dermatitis with leonine facies and iatrogenic adrenal insufficiency successfully treated with topical tacrolimus. Case Rep Dermatol 2011;3(1):49–54. 47. Ma Y, Lu Z. Treatment with topical tacrolimus favors chronic actinic dermatitis: a clinical and immunopathological study. J Dermatolog Treat 2010; 21(3):171–7. 48. Larangeira de Almeida H Jr. Successful treatment of chronic actinic dermatitis with topical pimecrolimus. Int J Dermatol 2005;44(4):343–4. 49. Norris PG, Camp RD, Hawk JL. Actinic reticuloid: response to cyclosporine. J Am Acad Dermatol 1989;21(2 Pt 1):307–9.
50. Gardeazabal J, Arregui MA, Gil N, et al. Successful treatment of musk ketone-induced chronic actinic dermatitis with cyclosporine and PUVA. J Am Acad Dermatol 1992;27(5 Pt 2):838–42. 51. Murphy GM, Maurice PD, Norris PG, et al. Azathioprine treatment in chronic actinic dermatitis: a double-blind controlled trial with monitoring of exposure to ultraviolet radiation. Br J Dermatol 1989;121(5):639–46. 52. Leigh IM, Hawk JL. Treatment of chronic actinic dermatitis with azathioprine. Br J Dermatol 1984; 110(6):691–5. 53. Thomson MA, Stewart DG, Lewis HM. Chronic actinic dermatitis treated with mycophenolate mofetil. Br J Dermatol 2005;152(4):784–6. 54. Safa G, Pieto-Le Corvaisier C, Hervagault B. Recalcitrant chronic actinic dermatitis treated with lowdose thalidomide. J Am Acad Dermatol 2005; 52(5):E6. 55. Parodi A, Gallo R, Guarrera M, et al. Natural alpha interferon in chronic actinic dermatitis. Report of a case. Acta Derm Venereol 1995;75(1):80. 56. Rose RF, Goulden V, Wilkinson SM. The spontaneous resolution of photosensitivity and contact allergy in a patient with chronic actinic dermatitis. Photodermatol Photoimmunol Photomed 2009; 25(2):114–6. 57. Sugita K, Shimauchi T, Tokura Y. Chronic actinic dermatitis associated with adult T-cell leukemia. J Am Acad Dermatol 2005;52(2 Suppl 1):38–40. 58. Thomsen K. The development of Hodgkin’s disease in a patient with actinic reticuloid. Clin Exp Dermatol 1977;2(2):109–13. 59. De Silva BD, McLaren K, Kavanagh GM. Photosensitive mycosis fungoides or actinic reticuloid? Br J Dermatol 2000;142(6):1221–7. 60. Adachi Y, Horio T. Chronic actinic dermatitis in a patient with adult T-cell leukemia. Photodermatol Photoimmunol Photomed 2008;24(3):147–9. 61. Bilsland D, Crombie IK, Ferguson J. The photosensitivity dermatitis and actinic reticuloid syndrome: no association with lymphoreticular malignancy. Br J Dermatol 1994;131(2):209–14. 62. Norris PG, Newton JA, Camplejohn RS, et al. A flow cytometric study of actinic reticuloid. Clin Exp Dermatol 1989;14(2):128–31. 63. Ashinoff R, Buchness MR, Lim HW. Lymphoma in a black patient with actinic reticuloid treated with PUVA: possible etiologic considerations. J Am Acad Dermatol 1989;21(5 Pt 2):1134–7. 64. Thestrup-Pedersen K, Zachariae C, Kaltoft K, et al. Development of cutaneous pseudolymphoma following ciclosporin therapy of actinic reticuloid. Dermatologica 1988;177(6):376–81. 65. Jong CT, Finlay AY, Pearse AD, et al. The quality of life of 790 patients with photodermatoses. Br J Dermatol 2008;159(1):192–7.
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KEY POINTS
HISTORY
EPIDEMIOLOGY
Chronic actinic dermatitis (CAD), previously known as actinic reticuloid, photosensitivity dermatitis, photosensitive eczema, and persistent light reaction, is an immunologically mediated photodermatosis characterized by pruritic eczematous lesions of areas exposed to the sun.1–5 Haxthausen6 first described this condition in 1933 in a patient with hypersensitivity to light after intravenous trypaflavine, a photosensitizing dye. Actinic reticuloid and two milder forms of CAD, referred to as photosensitive eczema and photosensitivity dermatitis, were reported in 1969.7,8 By 1979, Hawk and Magnus9 had introduced the term “chronic actinic dermatitis,” but it was not until 1990, when Lim and colleagues10 suggested unifying the variants under the same name, that the term became widely accepted.11
CAD has been reported in the United States, Europe, Asia, and Africa, with increased incidence in the summertime when sun exposure is greatest.12–16 It commonly affects men older than 50 years who work or enjoy the outdoors. This condition can affect individuals of all skin types, although in the United States it is more commonly reported in persons with Fitzpatrick skin types V and VI.17–20 In patients seen in the United Kingdom, but not those examined in the United States or Japan, CAD can be associated with contact allergy or photocontact allergy to Compositae oleoresins, a group of airborne plant allergens, presumably caused by exposure through gardening.21–24 There is no familial inheritance. Association with human immunodeficiency virus (HIV) infection has been reported; as a group,
Disclosure Statement: No conflicts of interest. Department of Dermatology, Henry Ford Hospital, 3031 West Grand Boulevard, Suite 800, Detroit, MI 48202, USA * Corresponding author. E-mail address: [email protected] Dermatol Clin 32 (2014) 355–361 http://dx.doi.org/10.1016/j.det.2014.03.007 0733-8635/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
derm.theclinics.com
Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis characterized by pruritic eczematous lesions of sun-exposed areas. Evaluation should include histologic examination, phototesting, and laboratory workup, including human immunodeficiency virus (HIV) test and Sezary count. The most common action spectrum is ultraviolet B (UVB) plus ultraviolet A (UVA), although CAD may also be seen with UVB or UVA alone, or with a combination of UVB, UVA, and visible light. Management begins with strict photoprotection, topical corticosteroids, and topical calcineurin inhibitors. Other treatments with noted efficacy include oral prednisone, cyclosporine, azathioprine, and mycophenolate mofetil. Proper diagnosis and management are essential, as CAD can have a moderate to large impact on quality of life.
356
Paek & Lim these patients tend to be younger than CAD patients without HIV infection.25
PATHOGENESIS The pathogenesis of CAD has not been completely elucidated. The clinical and histologic features, the presence of mostly CD81 T cells in the dermis, and the pattern of adhesion molecule activation in CAD resemble allergic contact dermatitis.26 Thus, a mechanism of delayed-type hypersensitivity can be inferred. However, rather than an exogenous agent, the cutaneous antigen is likely endogenous and photoinduced. Though not proven, it is possible that a pathophysiology similar to that described in polymorphous light eruption (PMLE) also occurs in CAD.27 In normal healthy individuals, exposure to sunlight results in localized immunosuppression; therefore, there are no obvious clinical lesions even in the presence of photoinduced neoantigens in the skin. However, similarly to PMLE, it is possible that patients with CAD are less likely to be photoimmunosuppressed, resulting in a brisk response to the presence of ultraviolet (UV)-induced neoantigens in the skin, which manifest as cutaneous lesions. The antigenic molecule in CAD has been theorized to be DNA, which absorbs UV radiation and is the molecule thought to be involved in sunburn.27,28 The action spectrum for CAD is similar to that for sunburn, but at lower doses.29
DIAGNOSIS Clinical Manifestations Skin findings of CAD include eczematous and often lichenified pruritic patches and confluent plaques limited to sun-exposed areas of the scalp, face, neck, chest, arms, hands, and back, with
notable sparing of sun-protected areas, such as nasolabial folds, submental chin, upper eyelids, retroauricular areas, skin creases, and finger web spaces (Fig. 1). Acute flares are associated with erythematous patches and papules with fine scale on sun-exposed areas (Fig. 2). In severe cases, papules and plaques may occur on sunprotected sites, albeit to a lesser extent than on sun-exposed areas; rarely, erythroderma and hyperkeratosis of palms and soles may be observed (Fig. 3).30
Differential Diagnoses Conditions that may mimic CAD include drug eruption, allergic or photoallergic contact dermatitis, cutaneous T-cell lymphoma (CTCL),31 and connective tissue diseases (such as acute or subacute cutaneous lupus erythematosus). Careful history taking, examination of morphology and distribution of lesions, and appropriate photobiological and laboratory investigations are essential in arriving at the correct diagnosis (Table 1).32
Histology Pathologic examination of CAD demonstrates spongiotic dermatitis with lymphohistiocytic infiltrate and variable acanthosis. Atypical lymphocytes and exocytosis seen in some specimens may mimic histologic changes of CTCL. Papillary dermal fibrosis and a brisk infiltrate, both histologic signs of chronicity, may also be found. In severe cases the biopsy may show focal epidermal necrosis, papillary dermal collagen, fibrin deposition in the dermal-epidermal junction, and erosions.
Photobiological Evaluation Phototesting is recommended for further evaluation of suspected CAD. If a monochromator or
Fig. 1. Clinical features of chronic actinic dermatitis (CAD). (A) Erythema, lichenification, and scale on sunexposed skin. Note sparing of postauricular area. (B) Lichenification of sun-exposed sites, with sharp cutoff of sun-protected areas of the skin.
Chronic Actinic Dermatitis which are set to replace common incandescent lamps in Europe, may be a potential harmful source of UV radiation with prolonged exposure in patients with photosensitive conditions. These lamps contain mercury, which activates the phosphor-coated walls, emitting UV radiation in the UVB and UVA range. Patch testing and photopatch testing may also be considered if warranted by the history of the patient. Patients with CAD in the United Kingdom often demonstrate positive patch testing to relevant Compositae, presumably resulting from exposure from gardening.
Fig. 2. Acute flare 24 hours after inadvertent sun exposure in a patient with CAD. Note diffuse erythema on the face and superficial erosions on the nose.
solar simulator is unavailable, testing with ultraviolet A (UVA; 320–400 nm) or ultraviolet B (UVB; 290– 320 nm) therapy units and a slide projector (to test visible light) may be considered.33 The most common action spectrum for CAD is UVB plus UVA, resulting in a decreased minimal erythema dose (MED) for both UVB and UVA in most patients.29,34 However, CAD may be seen with decreased MEDB or MED-A alone (12%–25%), or with a combination of sensitivity to UVB, UVA, and visible light. A study conducted by Eadie and colleagues35 also found that compact fluorescent lamps (CFLs),
Fig. 3. Hyperkeratosis and scale on palms of a patient with CAD.
Laboratory Evaluation Lupus serologies, such as antinuclear antibody (ANA) and anti-Ro/anti-La antibodies, may be obtained and should be negative. Sezary-like cells may be seen in erythrodermic CAD, but the CD4:CD8 ratio will be low and T-cell clonality will be absent.36 In addition, testing for HIV is recommended, especially in younger patients, in whom CAD may be a presenting sign of HIV.25
MANAGEMENT Strict photoprotection is key in the management of CAD.37 Patients should be advised to wear broadspectrum (UVA and UVB) sunscreen with a minimum sun-protection factor of 30, long-sleeved clothing, and wide-brimmed hats, and to seek shade during peak hours (between 10 AM and 4 PM). Clear museum films or UVA filters may be applied to windows to block most UV transmission.38 It should be noted that there is no evidence that television and computer screens might exacerbate this condition. In addition to photoprotection, patients may use topical corticosteroids or topical calcineurin inhibitors as first-line therapy. Mid-potency to highpotency topical corticosteroids are effective for the control of disease flare. However, the potential risks of skin atrophy, striae, and dyspigmentation preclude their long-term use. Many case reports and case series support the therapeutic benefit of topical tacrolimus 0.1% ointment, daily to twice daily, for CAD.39–46 Tacrolimus (Protopic) binds to FK506-binding protein, blocking dephosphorylation of nuclear factor of activated T cells, and preventing transcription of interleukin-2 and other inflammatory cytokines. In CAD, this seems to work by inhibiting T-lymphocyte activation by suppressing Langerhans cells.47 Similar results have been achieved with topical pimecrolimus (Elidel) cream for CAD.48 Patients must be informed of the black-box warning for increased risk of cutaneous malignancy and lymphoma with topical
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Table 1 Evaluation of chronic actinic dermatitis Test Histology
Results in CAD
Comments
Punch biopsy
Epidermal spongiosis with May be confused with CTCL. moderately dense superficial Immunohistochemistry and Tand deep lymphocytic infiltrate cell rearrangement warranted Phototesting UVA (320–400 nm) Decreased MED Most common action spectrum for CAD is UVB 1 UVA. May also UVB (290–320 nm) Decreased MED be seen with UVA or UVB Visible light May show decreased MED alone, or with a combination of (400–700 nm) UVB 1 UVA 1 visible light Laboratory Lupus serologies ANA, anti-Ro/-La negative Rule out other CTD Peripheral smear Sezary-like cells may be seen in Immunohistochemistry and gene erythrodermic CAD, but rearrangement analysis can be CD4:CD8 ratio will be low and conducted to further T-cell clonality will be absent differentiate CTCL from CAD HIV Negative CAD may be a presenting sign of HIV in younger patients. Testing recommended in high risk patients Abbreviations: ANA, antinuclear antibody; CAD, chronic actinic dermatitis; CTCL, cutaneous T-cell lymphoma; CTD, connective tissue diseases; HIV, human immunodeficiency virus; MED, minimal erythema dose; UVA, ultraviolet A; UVB, ultraviolet B.
tacrolimus and pimecrolimus, although convincing evidence is lacking. Systemic immunosuppressive therapy is frequently used for widespread or refractory disease. Oral corticosteroids (prednisone 0.5– 1.0 mg/kg/d) can be given for several weeks at a time for flares. Chronic steroid use is not recommended because of its adverse side-effect profile, including, but not limited to, weight gain, high blood sugar, increased risk for infections, osteoporosis, and fractures, adrenal gland suppression, delayed wound healing, glaucoma or cataracts, and steroid psychosis. Other steroid-sparing agents with proven efficacy in the treatment of CAD include: cyclosporine (3.5–5 mg/kg/d),49,50 azathioprine (1.0–2.5 mg/kg/d),51,52 and mycophenolate mofetil (25–40 mg/kg/d or 1–2 g/d).53 Patients should be counseled on the increased risk of infection with these medications. Additional potential side effects are noted in Table 1. Only single case reports exist to support the treatment of refractory CAD with low-dose thalidomide54 and interferon-a.55
PROGNOSIS Spontaneous resolution of chronic actinic dermatitis has been reported to be 10% over 5 years, 20% over 10 years, and 50% over 15 years.33 These findings were established from a historical cohort study of CAD patients in a Scottish tertiary referral center, and may underestimate the actual
probability of remission. Patients may be counseled that their photosensitivity may eventually subside with photoprotection and avoidance of allergens.56 In addition, a few case reports have suggested the possibility of malignant transformation of pseudolymphomatous CAD or association with other malignancies.57–60 However, a chart review of 231 patients with CAD enrolled in the National Cancer Registry of the United Kingdom identified no significant increased risk of lymphoma and nonlymphoma cancers in a 20-year study period.61 In addition, DNA flow cytometry of affected skin from patients with CAD did not demonstrate DNA aneuploidy.62 Therefore, it does not appear that CAD is a premalignant condition, but patients should be aware of the increased risk of malignancy with immunosuppressant therapy.63,64
SUMMARY CAD is an immunologically mediated photodermatosis characterized by pruritic eczematous and lichenified plaques sharply demarcated to sunexposed areas with notable sparing of eyelids, skin folds, submental chin, postauricular skin, and finger web spaces. It mostly affects men older than 50 years. The condition is thought to be due to secondary photosensitization of an endogenous antigen in the skin, resulting from either crossreactivity with other contact allergens or photocontact allergens, or the lack of localized
Chronic Actinic Dermatitis
Table 2 Management of chronic actinic dermatitis Therapy
Dosage
Comments
Strict photoprotection
—
Broad-spectrum (UVA/UVB-block) sunscreen Topical tacrolimus (Protopic) ointment
Minimum SPF 30
Long-sleeved clothing, widebrimmed hats, sun avoidance during peak daylight hours (10 AM to 4 PM), UV filters or museum film for windows inorganic filters
Prednisone
0.5–1.0 mg/kg/d
Cyclosporine
3.5–5 mg/kg/d
Azathioprine
1.0–2.5 mg/kg/d
Mycophenolate mofetil (CellCept)
25–40 mg/kg/d (1–2 g/d)
0.1% daily to BID
Black-box warning: increased risk of cutaneous malignancy and lymphoma For acute flares only Potential side effects: weight gain, high blood sugar, high blood pressure, increased risk of infections, osteoporosis, and fractures, adrenal gland suppression, delayed wound healing, glaucoma or cataracts, steroid psychosis Side effects: gingival hyperplasia, hypertrichosis, headache, nausea, malaise, gout, hyperkalemia, hypomagnesemia, hypertension, nephrotoxicity, malignancy Side effects: myelosuppression, hypersensitivity syndrome, GI symptoms, infection, lymphoproliferative malignancy Side effects: GI upset, teratogenic, carcinogenic, neurologic symptoms (headache, tinnitus, weakness), increased risk of herpes zoster, risk of hepatotoxicity
Abbreviations: BID, twice daily; CAD, chronic actinic dermatitis; GI, gastrointestinal; SPF, sun-protection factor; UV, ultraviolet; UVA, ultraviolet-A; UVB, ultraviolet-B.
photoimmunosuppression in such patients. Histology shows epidermal spongiosis with moderately dense superficial and deep lymphocytic infiltrate, which may be confused with CTCL. The most common action spectrum for CAD seen with phototesting is UVB plus UVA. As appropriate, patch testing and photopatch testing should also be performed. Laboratory workup should be aimed at excluding other potential diagnoses, such as CTCL and acute or subacute cutaneous lupus erythematosus. CAD may be a presenting sign of HIV in young patients with risk factors. Table 2 outlines the therapeutic management of patients with CAD. Spontaneous resolution has been reported to be 10% over 5 years, 20% over 10 years, and 50% over 15 years. Therefore, patients should be counseled that their photosensitivity may
eventually subside with avoidance of allergens and photoprotection. In addition, CAD does not appear to be a premalignant condition, but clinicians should provide counseling on the increased risk of malignancy with immunosuppressant therapy. Finally, CAD can have a moderate to large impact on quality of life, so proper diagnosis and management is essential.65
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