British Journal of Dermatology (1991) 125, 448-451.

The prevalence of antinuclear antibodies in patients with apparent polymorphic light eruption G.M.MURPHY AND J.L.M.HAWK Photobiology Department. St Thomas's Hospital, lA>ndon U.K.

Accepted for publication 1 7 June 1991

Summary

Polymorphic light eruption (PLE) is a very common photosensitive disorder, the most important differential diagnosis of which is lupus erythematosus (LE). One-hundred and forty-two patients with PLE were screened for circulating antinuclear (ANA). Ro and La antibodies over a 2-year period. Results were negative in 66 patients. Sixty-two patients had low-titre ANA of various patterns, ranging from trace to 1/80 without evidence of LE although one later developed subacute cutaneous LE. Fourteen had more significant findings, six with ANA ranging from 1/160 to 1/1280 but no antiRo antibodies, four with ANA ranging from 1/160 to 1/1280 and also with anti-Ro antibodies and four patients with anti-Ro antibodies but low-titre ANA, one of whom later developed discoid LE. Three of these 14 patients fulfilled the American Rheumatism Association criteria for the diagnosis of systemic LE, but it was not certain in any of the patients whether the PLE-like rash represented cutaneous LE or coincidental PLE. However the overall 10% incidence of definite or possible IJi in patients with suspected PLE suggests that all PLE patients should be screened for LE.

Polymorphic light eruption (PLE) is a common photodermatosis affecting 10-20% of the population' and may be a delayed-type hypersensitivity response to an ultraviolet (UV) radiation-induced cutaneous neoantigen. There is a dermal cellular inflammatory infiltrate and expression of intercellular adhesion molecule-1 (ICAM1) on keratinocytes which is consistent with that seen in delayed type hypersensitivity.^^ The diagnosis of PLE is based primarily on the typical clinical history, often in the absence of a visible rash, because the skin lesions are transient and many patients are not affected at the time of clinical presentation. Differential diagnoses suggested by the history alone include other photodermatoses and the light-exacerbated dermatoses and in particular lupus erythematosus (LE). It has therefore been our practice to exclude LE by routinely checking for antinuclear, antiRo and anti-La antibodies in all patients with apparent PLE presenting to the photobiology clinic. To determine the value of such screening we have now undertaken a retrospective study to assess the proportion of patients with an original presumptive diagnosis of PLE. based on clinical history aldne, who have eventually proved to have laboratory evidence of LE.

Methods Pathology records were studied over the 3-year period from January 1987 to December 1989. All request forms submitted during this time for assessment of antinuclear antibodies in patients with presumptive PLE who were seen in the photobiology clinics at St John's Hospital for Diseases of the Skin, London, were examined, the results noted, and the clinical notes retrieved to verify the original clinical diagnosis. With some patients, follow-up data of up to 2 years was available from the case notes. Because it was routine practice to screen all presumptive PLE patients for the possibility of LE, virtually all such patients during this time period were considered to have been included in the study. Antinuclear antibodies (ANA) were identified by indirect immunofluorescence on rat-liver sections. AntiRo (SSA) and La (SSB) antibodies were identified by counter-immunoelectrophoresis. Although not strictly quantifiable, the distance of the precipitate from the serum well (proportional to the amount of antibody present) was graded as trace, -I-, -f -I-, or + -I- -I-.

Results Correspondence: Dr Gillian M.Murphy. The Regional Dermatology Centre. Mater Hospital, Dublin 7. Ireland.

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One-hundred and forty-two patients with an original clinical diagnosis of PLE were identified. Results were

ANTINUCLEAR ANTIBODIES AND PLE

449

Table 1. Summary of clinical details. LE autoantibody status, and histological findings of patients with Ro antibodies

Patient

Age

Sex

Autoantibody

Histology

Clinical status

S.M. •V.H.

29 40

T.A. |.G. M.G. C.B. •P.K. C.B.

27 30 50 16

F F F

ANA 1 /20 Ro -f + + ANA 1 /20 Ro -f -f + ANA Trace Ro -i- -f ANA 1/10 Ro trace ANA 1/160 Ro +-)ANA 1/640 Ro -f -f La + -f -IANA 1/1280 Ro + + La -f + + ANA 1/160 Ro trace

No rash No rash Not done Typical of LE +IF

Three episodes typical PLE referred to St John's for PUVA Arthritis, malar rash, 8 years Hx PLE. FH PLE 5 years Hx and FH PLE, typical PLE rash present PLE 11 years. DLE on nose for 1 year 8/12 Hx typical PLE

47 42

F F M F F

No rash Vasculitis No rash No rash

1 year Hx PLE. PLE-like rash present 2 year Hx and FH PLE livedo. arthralgia. wcc 3 2 year Hx typical PLE

Hx, clinical bistory; FH. family history; IF. direct immunofluorescence. *. SLE.

negative in 66 patients (mean age 35 years, range 8-63 years). Of the remaining 76, 62 had ANA of various patterns, ranging from trace amounts to titres of 1/80 (mean age 35 years, range 11-65 years). The other 14 had more significant findings: six with ANA ranging from 1/160 to 1/1280 but no anti-Ro antibodies: four with ANA ranging in titre from 1/160 to 1280 and also with anti-Ro antibodies, three of them strongly positive and two also with anti-La antibodies: and four with antiRo antibodies but with low-titre ANAs ranging from trace amounts to titres of 1/20. The clinical details of those with positive ANA and anti-Ro antibodies are summarized in Table 1 and those with significantly positive ANA and negative anti-Ro in Table 2. Skin biopsies were carried out on five of the 14 patients with significant findings, and in one patient with ANA 1/10 and a persistent rash suggestive of LE. The remainder had not undergone skin biopsy because the rash was not present at the time of assessment (seven patients) or because the rash was considered so typical of PLE that biopsy was not thought necessary (two patients). Direct immunofluorescence was carried out in

four of the six patients biopsied. Definite histological features of LE were present in four patients (Tables 1 and 2): one with ANA 1/10 and trace positive anti-Ro who developed discoid LE on the nose 10 years after developing a rash typical of PLE: another with ANA 1/640. strongly positive ribonucleoprotein (RNP) and negative anti-Ro antibodies who had skin histology typical of LE: a third with ANA 1/320 and negative anti-Ro who fulfilled the American Rheumatism Association criteria for SLE and whose skin biopsy demonstrated the typical histology of LE: and a fourth with ANA 1/10 but negative anti-Ro antibodies who was subsequently thought to have subacute cutaneous LE both clinically and histologically. A further patient, a 16-year-old boy, was thought clinically at first presentation to have persistent lesions of PLE: however, with an ANA of 1/ 640 and a strongly positive anti-Ro antibody titre together with histological evidence of leucocytoclastic vasculitis, the diagnosis of cutaneous LE was considered likely and he has since been well controlled with mepacrine (T. Cutler, personal communication). Three of the 14 patients had evidence of systemic

Table 2. Summary of clinical, immunological and histological investigations in patients with negative Ro antibodies but positive ANA

Patient

Age

Sex

E.G. H.W. E.Y. R.S. F.N. •V.N. S.B.

41 61 45 64 65

F F

45 29

F M F F F

Autoantibody ANA ANA ANA ANA ANA ANA ANA

1/1280 1/320 1/160 1/640 RNP + + + 1/320 Thglb 1/100 1/320 1/10

Histology

Clinical status

No rash No rash Not done Typical LE Compatible with PLE - I F Typical LE - I F SCLE +IF

8 years Hx typical PLE. referred for PUVA Typical PLE. tolerance by autumn 4 years Hx typical PLE 8 years Hx PLE Sun rash since age 12. hypothyroidism PLE 4 years, rash, alopecia, arthritis, malaise PLE for 4 years, developed SCLE-like rash

Thglb, tbyroglobulin; SCLE. subacute cutaneous IE: Hx. clinical history; IF. direct immunofluorescence; *. SLE.

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G.M.MURPHY AND J.L.M.HAWK

involvement. One patient had a malar rash and arthritis, a second had proteinuria, arthralgia, livedo reticularis and a white cell count of 3 x lO'/l (Table 1), and a third had malar rash, alopecia, arthritis, malaise and positive skin histology (Table 2). These patients all fulfilled the 1982 revised American Rheumatism Association criteria for systemic LE* because of their systemic involvement, photosensitivity and positive ANA, although all three had mild disease, anti-DNA antibodies within the normal range and no renal impairment.

Discussion Lupus erythematosus affecting the skin is classified into acute LE, subacute cutaneous LE, chronic discoid LE and lupus profundus.' Although photosensitivity is a wellrecognized feature of all types of LE, it is most frequently associated with subacute cutaneous LE in which the majority of patients have circulating anti-Ro antibodies.'' The rash, classically linked with subacute cutaneous LE, is a papulosquamous polycyclic or psoriasiform eruption, which often persists for weeks in the absence of treatment.'' Other forms of lupus may also be photosensitive.'^"'" for example neonatal LE, a consequence of passive maternal transmission of anti-Ro antibodies and chronic discoid LE,^ in which UVirradiation of the skin produces papuiosquamous lesions in 50% of photosensitive patients.' Photosensitive lupus is unlikely to be confused with PLE in patients with established LE. but it is now clear that some cases of LE presenting with only a transient photosensitive rash cannot always be definitely distinguished on clinical grounds alone from PLE. In most PLE patients the morphology of the eruption is not seen at clinical consultation and because the time courses and morphology of both the LE and PLE rashes are often similar, the two conditions may be confused. Thus of 142 patients presenting with a transient photosensitive rash indistinguishable from PLE. we have found that 15 had significant abnormalities confirming or strongly suggesting the diagnosis of LE. Three had SLE, one later developed DLE and one SCLE, one had leucocytoclastic vasculitis, photosensitivity and strongly positive ANA and anti-Ro antibodies making the likelihood of LE great and nine others had significantly abnormal ANA or Ro antibodies. Although in each case there is a strong possibility that the PLE-Iike rash represented lupus photosensitivity, it is also possible that in some or all of these patients the occurrence of two unrelated phenomena, namely LE and PLE. was coincidental, or that the high-titre ANA or Ro antibodies were

occasionally spurious findings. Against the latter suggestion however is the fact that such high antibody titres are rarely seen in the general population. They are also virtually never seen in chronic actinic dermatitis, another photosensitive condition not resembling LE. in which it has been our practice to screen routinely for antinuclear and anticytoplasmic autoantibodies. The role of antinuclear and anticytoplasmic autoantibodies in the pathogenesis of the photosensitivity of LE is unresolved. Anti-Ro antibodies are related temporally to the appearance and disappearance of the photosensitive rash of neonatal LE.''" UVB-irradiation of cultured normal keratinocytes'^' ^ and human skin in wvo'* leads to expression of Ro antigen on the cell surface, probably leading to cytotoxic effects.'^ Anti-Ro antibodies are known to be associated with subacute cutaneous LE,'' neonatal LE," C2 and C4 deficiency''"' and ANAnegative LE, all characteristically photosensitive disorders. Efforts to associate the presence of circulating ANA with epidermal damage have not been rewarding.'^"* This may be because UV irradiation is also necessary to alter skin antigenically, immunoreactants being frequently detected in chronically light-exposed areas in SLE." However, UV irradiation of genetically susceptible mice and humans induces or exacerbates LE.-" In order to clarify whether our group of apparent PLE patients with high-titre ANA or Ro antibodies have LE, further cutaneous UV provocative studies are underway to asssess whether differentiation from ANA- and Ronegative PLE is possible. Long-term follow-up of the patients is also being undertaken to define more fully the disease course and prognosis.

Acknowledgment We are most grateful to Ms Jill Gilroy, The Autoimmune Serology Laboratory, The Academic Department of Immunology, Royal Free Hospital, London, who did the autoantibody studies and provided details of methodology.

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The prevalence of antinuclear antibodies in patients with apparent polymorphic light eruption.

Polymorphic light eruption (PLE) is a very common photosensitive disorder, the most important differential diagnosis of which is lupus erythematosus (...
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