Clinical and Experimental Dermatology 1992; 17: 38-43.

Chronic actinic dermatitis with vitiligo-like depigmentation p.VON DEN DRIESCH, M.FARTASCH AND O.P.HORNSTEIN Department of Dermatology, University Erlangen-NUrnberg, Erlangen, Germany Accepted for publication 27 April 1991

Summary This report describes two patients suffering from severe chronic actinic dermatitis. Unusual widespread vitiligolikc depigmentation occurred during the course of the disease. The progression of these lesions was triggered by the chronic actinic dermatitis. Loss of pigment and complete absence of tyrosinase positive melanocytes were found in depigmented skin of both cases. Immunohistological investigation ofthe intlammatory infiltrate in case 2 revealed a predominance of CD-S positive cytotoxic/suppressor lymphocytes. Analysing the adjacent pigmented epidermis of progressive depigmenting lesions a dense exocytosis of CD-8 F-eells was notable. This distribution suggests cytotoxic destruction of melanocytes as the cause for the \itiligo-like depigmentation.

Chronic actinic dermatitis (CAD) is an uncommon disorder that aflfects predominantly older males and is characterized by chronic inflammatory lesions primarily in light exposed skin due to photosensitivity.' The unifying term CAD comprises such diseases as persistent light reactions,- chronic photosensitivity eczema' and actinic reticuloid"^ which have clinical and pathogenetic similarities.' This article describes two patients suffering from CAD with widespread vitiligo-like lesions. As additional cases with similar depigmentation associated with CAD have been reported in thepast,""''we discuss the possibility that such depigmentation may appear more frequently in CAD compared to other inflammatory skin disorders and a specific mechanism may account for the occurrence of these lesions. Recent immunohistologcal investigations revealed CD8 positive T-lymphocytes as the predominant inflammatory cells in most cases of CAD.'"" Our immunohistological and histochemical analysis of the infiltrating inflammatory cells and melanocytes in pigmented versus Correspondence: Dr von den Driesch, Dermatologische Lniversitatsklinik, Hartmannstr. 14, 0-8520 Krlangen, Germany.


depigmented skin of case 2 support the hypothesis that the destruction of melanocytes may be caused by these CD-8 positive., probably eytotoxic T-lymphocytes.

Case reports Case I

A 77-year-oId patient, formerly a farmer, had suffered from severe eczematous lesions on light exposed skin since 1967. In 1970 he noticed the first appearance of depigmentation on face, neck (Fig 1-3) and forearms. In 1972 the diagnosis of persistent light reaction and vitiligo was confirmed at our hospital. From 1970 to 1983, several treatments were necessary to control acute exacerbations of the CAD. Histopathological examination of several biopsies revealed chronic eczematous inflammation. Phototesting (performed with PUVA 3001, Waldmann, Schwenningen, FRG; broad band UVA, maximum at 360 nm) elicited eczematous reactions with minimal UVA doses ranging between 2 and 5 J/cm' (Fig. 2). Patch tests revealed type IV reactions to potassium dichromate, resorcine and thioglyccrine. No photoallergy could be elicited by photopatch tests. Silver staining and DOPA-reactivity'' of pigmented versus depigmented skin revealed a regular distribution of melanocytes and of melanin pigment in normal skin compared to depigmented skin which showed neither pigment deposition nor melanocytes. Immunohistology was not performed in this case. Different treatments failed to maintain long-lasting remissions until 1983 when oral methoxypsoralen photochemotherapy (PUVA) was started. Two h after oral administration of 40 mg psoralen (0-5 mg/kg body weight) UVA radiation, initially at a dose of 01 J/cm', was given to the entire body thus avoiding oral medication with steroids. In the following 10 weeks the UVA doses were increased at a rate of 01 J/week up to lOJ/cm' at which stage complete clinical remission was achieved. After a total UVA dose of 16-5 J/cm^ the patient was able to tolerate UVA-doses up to 20 J/cm^ and outdoor light


1. t^ase 1: V'itiligo-Iike depigmentation on the face after the remission of C^AI).

exposure for 2 hours.'' A stable (follow-up 12 months) remission was achieved with continuous PUVA therapy for 7 months. '^e 2 This 81-year-old patient was admitted to our hospital for the evaluation and treatment of a long-lasting erythroderma with progressive cachexia. Severe inflammatory and itehy lesions had appeared on his face and forearms 1 year before and the diagnosis of acute photoallergic/ phototoxic dermatitis had been established. No causative phototoxic or photoallergic agent had been discovered from the patient's medical history. During the following months the disease had run an erythrodermic course becoming increasingly resistant to therapy. Along with this disease the patient noticed the appearance of depigmentation on his face and arms which rapidly spread to t)ther skin areas. Physical examination revealed a dry and scaly melanoerythroderma with advanced cachexia (body weight 40


Figure 2. Case 1: Complete depigmentation f)f ihe neck alter the remission of ( . . \ n . Kczematous reactions on L"\'A phototests ranging from 2 to 9 J/cni' on the back.

kg). The inflammation was more prominent on sunexposed skin sites (I'ig. 4a). Generalized enlargement of lymph nodes was noted. In addition multilocal vitiligolike depigmentation of wide areas of skin including face, arms., trunk and legs were noted (Fig. 4b,c). These lesions were sharply and irregularly bordered and were confluent in sun-exposed areas. Investigations including routine serum profile, haematological examination as well as chest X-ray, abdominal sonography, computed tomography of the abdomen, upper Gl-endoscopy, coloscopy and bone scintigram did not reveal an underlying neoplasm. Diseases of the thyroid and Addison's disease were also excluded. Patch tests showed type-IV reactions to nickel sulphate and potassium dichromate. Photopatch testing was not performed due to extreme light sensitivity. Phototests (Multitester, Saalmann, Herford, FRG with separated broad band UVA, maximum at 360-380 nm, and broad band UVB, maximum at 310 nm) revealed marked localized eczematous reactions at minimal doses



P'igurc 3. t^ase 2: CAD presenting a:5 a chronic ii!L'lanoer\ throderma with advanced cachexia. Vitiligo-like depigmentation on face, breast and arms.

of IS J/cm- UVA and 0 007 J/cm^ UVB. These results were reproduced twice after a remission of erythroderma. Examination of several routinely processed skin biopsies revealed an acute eczema with a dense, predominantly lymphocytic infiltration of the upper dermis and spongiform exocytosis not suggestive of a cutaneous Tcell lymphoma. Examination of an axillary lymph node showed dermopathic lymphadenopathy, again without any evidence of a lymphoproliferative disease. Silver staining and Dopa-reaction revealed similar results as in case 1. A sharp border between pigmented and depigmented epidermis (Fig. 5) was found using biopsies from across the borderline. Tn contrast to case 1 melanophages, especially in the depigmented areas, were strongly stained with both methods indicating the presence of pigment and some phagocytosed intact enzyme complexes suggesting acute destruction of melanocytes. This phenomenon was also evident in the adjacent, still normally pigmented skin indicating progression of the melanocytolytic process. For therapy, the patient was hospitalized in a darkened

Figure 4. Sharp borderline between pigmented and depigmented skin, (a) Clinically on the lower hack and thighs; (b) histologically after staining witb DOPA. Subepidermal staining demonstrates the presence of fresbly phagocytosed tyrosinase complexes in melanophages.

room and continuous amelioration of the erythroderma was achieved within 3 weeks. His general health improved and body weight increased to 45 kg. PUVA treatment was then performed as outlined for case 1 (30 mg 8-methoxypsoralen) and he maintained a stable remission (follow-up 10 months). Immunohistological results of case 2 Immunophenotyping of the cellular inflltrate was performed on a snapfrozen oval excision covering both depigmented and adjacent pigmented eczematous skin. Immunostaining was accomplished using the monoclonal antibodies Leu-2a, Leu-3a, Leu-4, I,eu-M3 and I,eu-12 (Becton-Dickinson, Mountain View, CA, USA) as well as OKM-1 and OKM-5 (Ortho Pharmaceutical Corp., Raritan NY, USA) and the immunoperoxidase method as described elsewhere.'"' Sequential .sections were stained with DOPA in order to differentiate pigmented from


P.VON DKN DRIESCH, M.FARTASCH AND O P.HORNSTEIN Table 1. Two patients witb CAD and vitiligo-like de pigmentations Patient 2

Patient 1 Age Sex

77 years Male

81 years Male

I'or 14 vears 2-5J,'cmPotassium dichromaie. tbioglycerine, resorcine Negative F.czeniatous

For 1 year

CAD Appearance U V A-phototesting Patch tests Photopatch Histo!og\ Immunohistology

ND l.n\K dosr-PlVA

Depigmentaiion Appearance Prt)gression Lesions Sites Silver staining DOPA reaction

l-8J/cm^ Potassium dichromatc. nickel sulphate \D

l''.czeniatous Predominance ol'T-Umphocyte infiltration CD4/CDS ratio 0-8 Low dose-PUVA

r-'or 14 years l'or 7 month Slower Rapid Strictly sharp-demarcaied, bizarre polycyclic vitiligo-like Preferred CAD involved areas of skin, no involvement of ptrianal or perigemia! skin Sharp border between pigmented and depigmented areas of skin, subepidermal pigmcni containing melanophages on!\ in case 2 Normal melanocyte distribution in pigmcnied skin, no tyrosinase positive melanocytes in depigmented skin, positive subepidermal niclanophnges in

7. Haynes IIA, Bernhard JD, CJangc RW. Actinic reticuloid response to combination treatment with azatbioprine bydrowchloroquine and prednisone. /'^///'MI// ofthe .tiiicrican Icudemy oJ Dermatology I9S4; 10: 947 9.S2. IS. Kaidbey KH, Messenger JL. The clinical spectrum of the persistent light reactor. Archives of Dermatology 1984; 120: 1441 1448. 9. Toonstra J, van Weelen H, Gmelig Meyling FlIJ, van der Putte SCJ et al. Actinic reticuloid simulating Sezary Syndrome. Archives of nermatohgicul Research 19S.i; 277: IS") lf>6. 10. Toonstra J, van der Putte SCJ, van Wichcn Dl" et al- Actinic References reticuloid; imniunobistocbeniical analysis {>f tbe cutaneous infiltrate in 13 patients, British Journal of Dermatology 19S9; 120:779 1. Hawk JLM, Magnus IA. (.Chronic actinic dermatitis an idio7S(., patbic photosensitivity syndrome including actinic reticuloid and phott)sensitivity eczema. British Journal of Dermalology 1*)7"J; 101 11. Norris PG, Morris J, Smith NP et al. CbronJc actinic dermatitis; An immunohistological and photobiologic study. Journal ol the (Suppl, 17): 24. •Imerican Academy of Dermatology 1989; 21; 966 971. 2. Jillson OF, Baughman RD. Contact photodermatitis from bithio12. Bolognia JL, Pawelek JM. Biology ofbypopigmentation./"///-//,// nol. Archives of Dermatology !9().3; 88: H13 112. ofthe American .icademy of Dermatology 1988; 19: 217-255. 3. Frain-Bell W, Lakshniipathi T, Rogers J, Willock J. The syndrome of chronic photosensitivity dermatitis and actinic 13. Von den Driescb P, Simon M Jr, Lccbner T, llornstein OP. Modifizierte PUV.A-Tberapie bei scbwerer persistierender Lichreticuloid. British Jnuriuil of Dermatology 1D8 positive T-lymphocytes, yet the exocytosis was weaker and the basal layers of the epidermis were not markedly infiltrated.

The pathogenesis of chronic actinic dermatitis (persistent light reactions, actinic reticuloid or chronic photosensitivity syndrome) has not yet been completely elucidated.'^ Agents known to cause type-IV-photoallergy as well as phytoallergens have been recognized as possible inducers via photoallergic/phototoxic contact dermatitis and persistent photosensitivity. "• Persistent light induced alteration of the carrier protein of the original photoallergen resulting in a continuous light dependent antigenic stimulation is one possible hypothesis.'' Both our patients had type-IV-allergy to potassium dichromate. Allergies to metal salts have been observed more frequently in patients with CAD,'' yet their pathogenic relevance is still unclear. A particular clinical feature of both cases was the occurrence of widely distributed vitiligo-like depigmentation (Table 2). Apparently, the CAD had triggered this phenomenon as it began in sun-exposed areas and then spread. One might speculate that these lesions represent only normal postinflammatory loss of pigment well known in many intlammatory skin disorders.'' The clinical appearances., however, were characteristic of classical vitiligo, showing sharp demarcation and bizarre polycyclic borderlines. Additional case reports (6-9) substantiate our view that vitiligo-like depigmentation may occur more frequently in CAD than in other forms of chronic eczema of comparable extent. These lesions were interpreted as post-inflammatory hypopigmentation, however detailed analysis was not performed. Our immunohistological and histochemical studies in case 2 focused on adjacent, clinically normal pigmented areas of a progressively depigmented lesion. DOP.\ reactivity of melanophages in these sites pointed to the beginnings of destruction of meianocytcs. .An unusual immunohistological feature distinguishing pigmented and depigmented sites was the ditlerent distribution of (^D8 bearing T-cells. Epidermotropism was generally enhanced and a characteristic single-cell exocytosis of lymphocytes into the melanocyte bearing ba.sal layers of pigmented epidermis was .seen. This pattern suggests close cell to cell interactions between presumed cytotoxic lymphocytes and melanocytes. According to this view cytotoxic CD8 bearing T-lymphoeytes are primarily activated as a result of CAD and may then contact melanocytic autoantigens leading to the destruction of melanocytes. The frequent occurrence of secondary depigmentation in CAD may therefore be a result ofthe action of CD8 T-cells.'"" This may be a unique feature of CAD-induced depigmentation. However, pathogenetic parallels may also exist in some types of classical vitiligo, since Haider^/ (//. have reported signiticantly increased levels of CD8-

CHRONIC ACTINIC l(), .Addol I.\, Frain-Bell W. Persistence of allergic contact sensirivitv in subjects with photosensitivity dermatitis and actinic reticuloid s\ndrome. British Journal of Dermatology 1987; 117: 555 559. 17. 1 lannukscLi \ I , Suhonen R, I'"6rstr6ni L. Delayed contact allergies in patients witb photosensitivity dermatitis. Acta Dermato-l eneieologica (Slockholm) 19X1; 61; .SD.V M)b. IS. Haider RM, Walters CS, Johnson BA, C:hakribati SG ct al. .Aberrations in T lymph(x:ytes and natural killer cells in vitiligo: A flow cytometric stud\. Journal of the American Academy of Dermatology 1*)86, 14: 733-737. IM, ^ {)kel BK,, Hood ,'\1', Morison WL. Management of chronic photosensitive eczema, irchives of Dermatology 1990; 126: 12831285. 21), llol/lc I'., Ilofmann C, Plewig G. PUVA treatment for solar







urticaria and persistent light reaction. .Archives oJ Dermalological Research 1980; 269: 87

Chronic actinic dermatitis with vitiligo-like depigmentation.

This report describes two patients suffering from severe chronic actinic dermatitis. Unusual widespread vitiligo-like depigmentation occurred during t...
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