Chronic cutaneous lupus erythematosus presenting as periorbital edema and erythema Stanley Cyran, M D , Margaret C. Douglass, MD, and Judith L. Silverstein, M D
Detroit, Michigan We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs. (J AM ACADDERMATOL 1992;26:334-8.)
Although facial involvement in chronic cutaneous lupus erythematosus ( C C L E ) is common, eyelid involvement as the sole manifestation of C C L E is rare. W e present two cases of eyelid edema and erythema as the sole manifestation of C C L E and review the literature. CASE REPORTS Case 1 A 5 l-year-old white woman had a 3- to 4-month history of asymptomatic left-sided eyelid edema and erythema. She was otherwise well. A prior ophthalmologic examination and plain films of the sinuses revealed no abnormalities. Results of routine laboratory studies were negative. Testing for antinuclear antibodies (ANAs) was positive at a titer of 1:160 in a speclded pattern. A course of sulfacetamide eyedrops had been of no benefit but several brief courses of oral prednisone provided temporary improvement. The patient had two sisters with lupus erythematosus (LE), one of whom died of complications of her disease; the other may have had only cutaneous involvement. Examination revealed marked left eyelid edema and erythema with slight crusting of the upper eyelid (Fig. 1). A repeat test for ANA was positive at 1:140 (HEp-2 cells) in a homogeneous pattern. Anti-double-stranded DNA was negative, anti-Ro (SSA) was positive, and anti-La (SSB), anti-RNP, and anti-Sm were negative. A chest x-ray film was normal and a computed tomographic (CT) scan of the orbit showed only mild soft tissue swelling of the left malar area. Patch testing to the 20 standard antigens of the American Academy of Dermatology From the Department of Dermatology,Henry FordHospital. Reprint requests:Margaret C. Douglass,MD, Departmentof Dermatology,2799W. Grand Blvd.,Detroit, MI 48202. 16/4/3~48 334
(AAD) panel (Allergen Patch Test Kit, Hermal Kurt Herrmann, Reinbeck, Germany) was negative. A skin biopsy specimen showed mild hyperkeratosis, diffuse epidermal atrophy with focal erosion and focal vacuolization of the basal cell layer of the epidermis, and infundibular follicular epithelium with occasional Civatte bodies. The dermis showed edema, telangiectases, and a moderately dense, superficial and deep perivaseular and focally perifollicular lymphohistioeytic infiltrate that contained a few plasma cells (Fig. 2). Direct immunofluorescence showed granular deposition of IgG, IgM, IgA, and C3 along the basement membrane zone (Fig. 3). Quinacrine was started at a dose of 100 mg per day. After 5 weeks there was marked improvement in the eyelid erythema and edema; however, the drug was discontinued because of a generalized drug eruption. Ten months after therapy was discontinued the patient's eyelid edema and erythema remained in remission. Because of her history of thyroid disease, thyroid studies were obtained, which showed a low normal T4, an elevated thyrotropin at twice the upper limit of normal, and markedly elevated thyroid antimicrosomal and antithyroglobulin antibodies at l:1600 and 1:6400, respectively. These values were consistent with a diagnosis of autoimmune thyroiditis, and thyroid replacement therapy was started. Case 2 A 45-year-old white woman had asymptomatic, intermittent left eyelid edema and erythema in August 1988. An ophthalmologist diagnosed "nasolacrimal duct obstruction." A left nasolacrimal stent was placed with no improvement. A C T scan of the orbit revealed only leftsided eyelid edema. Subsequently, a dacryocystorhinostomy and medial and anterior orbit exploration and biopsy were performed. The specimen revealed fibromuscular tissue with a lymphohistiocytic infiltrate. Patch testing to fiberglass and cellulose to which the patient was
Volume 26 Number 2, Part 2 February 1992
CCLE presenting as periorbital edema and erythema 335
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Fig. 1. Patient 1. T,e~teyelkl edema and eryfl~ema, with slight crusting. Fig. 2. Patient 1. LGt eyelid. Diffuse epidermal atrophy, ~oc~lbasal vacuolopathy, dermal edema, and dense peri~ascular ~nd pefifolHcular [ymphohistiocy~ic infiltrate. (• basement m~brane zone. (Fluor~ccin isothiocyanate; • Fig. 4. P~tient 2. Bilater~! eydk] edema and erythema. Fig. 5. Patient2. Leftlowereyelid. Epidermalatrophy, focalbasalvacuolopathy, anddense perivascular and perifollicular lymphohistiocytic infiltrate. (•
"~"
336
Cyran et aL
exposed as a shipping clerk was negative. Several courses of oral prednisone provided temporary improvement but the edema and erythema recurred intermittently. Right eyelid edema and erythema developed approximately 1 year later. Bilateral anterior orbitotomies with excisional biopsies of orbital contents and skin biopsies of both lower eyelids were performed. These revealed lymphohistiocytic infiltration of the adipose tissue and fibromuscular tissue of the orbits and a perivascular and papillary dermal Iymphohistiocytic infiltrate in the eyelid specimens. The patient was referred to the Henry Ford Hospital Departrnent of Dermatology in November 1989. She had bilateral eyelid edema and erythema (Fig. 4). Results of routine laboratory studies were negative. Testing for ANA (HEp-2 cells) was negative as was testing with antibodies to Ro (SSA) and La (SSB). Patch testing to 20 standard antigens and the brown paper wrapping that she used at work was negative. A biopsy specimen from the left lower eyelid showed epidermal atrophy with hydropic degeneration and multiple eosinophilic globules. In the dermis there was a pedvascular and periadnexal iymphohistiocytie infiltrate (Fig. 5). Direct immunofluorescence staining revealed globular fluorescence along the dermoepidermaljunction with IgG, IgM, IgA, and C3. The patient was treated with hydroxychloroquine, 200 rag/ day, and showed mild improvement. Her dose was increased to 400 rag/day after 2 months and prednisone was added at an initial dose of 40 mg/day. After 2 more months the erythema and edema were nearly completely resolved and therapy was discontinued. She has remained in remission for 8 months.
'DISCUSSION Periorbital edema has been reported in patients with systemic lupus erythematosus (SLE). 1~ Tuffanelli and Dubois jt reported a 0.1% incidence of periorbital edema as the presenting manifestation of SLE and an overall incidence of 4.8%. In a review of these articles, it appears that the authors were using the term periorbital edema synonymously with eyelid edema. Unilateral proptosis has also been described in LE, and in one case report it appeared to coincide with the progression of localized cutaneous to systemic disease. 12 In our cases, there was no evidence of systemic involvement or progression to SLE. In their description of the "discoid" form of localized lupus erythematosus (DLE), Hebra and Kaposi 13 included the eyelids as a site of involvement. Several subsequent reports have mentioned the eyelid as a potential site of cutaneous involvement of the lesions of DLE. 7, 8,14 We have found 21 cases in the English-language literature of L E limited to the skin
Journal of the American Academy of Dermatology
with lesions involving, or limited to, the eyelids.15-25 In these case reports, the lesions were variously described as marginal blepharitis, usually with loss of cilia, or as infiltrated plaques, with characteristic "discoid" features of atrophy, scarring, telangiectasia, and follicular plugging. In only two of these case reports, however, did the eyelid findings consist solely of edema. Both patients were A N A negative. In one patient, the edema was bilateral but associated with an additional discoid plaque involving the skin of the supraorbital ridge. 2~ Evidence of lupus panniculitis was also seen. In the other patient it was unilateral and the sole cutaneous finding. 22 In that patient, SSA antibodies were negative, and direct immunofluorescence showed IgG, IgM, complement and fibrin deposition at the DE junction with the presence of cytoid bodies. Our first patient was positive for anti-Ro (SSA) antibody. Although this antibody is present in 30% to 40% of patients with SLE, 2 it is also present in approximately two thirds of patients with subacute cutaneous lupus erythematosus (SCLE). 26 Because her cutaneous eruption was nonscarring, it m a y be appropriate to consider it as a variant of SCLE. However, the eruption did not have the characteristic papulosquamous or annular polyeyclic appearance and the patient lacked any other evidence of systemic disease. In addition, patients with S C L E typically have arthritis or arthralgias, and up to half fulfill at least four of the American R h e u m a t i s m Association's criteria for SLE. 27 We are using the term chronic cutaneous lupus erythematosus to refer to the particular subset of LE into which our patients fall. Their disease is limited to the skin but the lesions lack the features of atrophy, scarring, and follicular plugging associated with the discoid form of cutaneous LE. In our second patient, direct immunofluorescence testing showed deposition of immunoglobulin and complement in a globular pattern. This globular pattern, consisting of ovoid "hyaline" bodies, although not specific for LE, has been described in the subepidermal papillary regions and epidermis in LE.28, 29 The hyaline bodies have been postulated to arise from epidermal cells and basement membrane. 3~ This pattern has also been described in lichen planus, mycosis fungoides, and dermatomyositis. 31 Our second case illustrates the difficulty in making the diagnosis of LE when the disease is limited to the eyelids. In the case reports of LE with eyelid
Volume 26 Number 2, Part 2 February 1992
CCLE presenting as periorbital edema and erythema 337
involvement the average duration until the time of diagnosis was 3 years. The average time until diagnosis in the patients with eyelid erythema and edema only, including our two patients, was 2 years. The appearance of an inflammatory infiltrate in fragments of orbital adipose tissue in our second patient suggests the possibility of lupus panniculitis, which may occur in association with CCLE. 32 Seven of the 21 patients reported with cutaneous LE limited to, or involving, the eyelids were treated with chloroquine (on of these with chloroquine in association with oral corticosteroids) and four with hydroxychloroquine.15-25 All but one of the patients treated with chloroquine improved, as did all of the patients treated with hydroxychloroquine. One patient was treated with intralesional steroids but the clinical response was not indicated. Our two patients responded to quinacrine or hydroxychloroquine. The edema in our patients probably results from the combination of loose areolar connective tissue in the periorbital area and the dermal edema that is a characteristic feature of the cutaneous lesions of LE.33, 34 Marks et al. 35 showed that capillary permeability is increased in inflammatory lesions of patients with collagen vascular diseases, and Gilje et al.36 have shown by capillary microscopy dilated capillaries and arterioles with exudation of serum into the surrounding tissues in erythematous lesions of LE. The presence of dermal mucin, which occurs in discoid LE, may also account for the edematous appearance of the lesions. 37 Our first patient demonstrated the association of autoimmune thyroiditis with CCLE. We know of no other reports of this association. However, SLE occurs in conjunction with other disorders characterized by autoantibody formation including autoimmune thyroiditis. Several reports have estimated the coincidence of these two disorders to be between 0.2% and 4%.38, 39 Miller et al.4~ recently studied 175 patients with SLE and found 45% with an elevated thyrotropin and 10.9% with thyrotropin greater than twice normal. Elevated and antithyroglobulin antibodies were found in 7.1% and 18.4% had elevated antimicrosomal antibodies. They concluded that 44% of these patients had either subclinical or biochemical primary hypothyroidism, which is much higher than the prevalence in the normal population. Although eyelid edema has been described in association with Hashimoto's thyroiditis, 41the characteristic histologic and immunofluorescence find-
ings in our patient favor LE as the cause of her clinical findings. REFERENCES 1. Callen JP. Chronic cutaneous lupus erythematosus. Arch Dermatol 1982;118:412-6. 2. Sontheimer RD, Deng J-S, Gilliam .IN. Antinuclear and anticytoplasmic antibodies. J AM ACADDERMATOL1983; 9:335-43. 3. Rook A, Wilkin DS, Ebling FJG, et al, eds. Textbook of dermatology. Oxford: Blackwell Scientific, 1986:2150. 4. Diestelmeier MR, Sausker WF, Pierson DL, et al. Sareoidosis manifesting as eyelid swelling. Arch Dermatol 1982; 118:356-7. 5. Roy FH. Ocular differentialdiagnosis. Philadelphia: Lea & Febiger, 1989:84-6. 6. Hollander L, Baer JL. The common disorders of the skin of the eyelids. Am J Ophthalmol 1935;18:616-23. 7. Long PR, Miller OF III. Linear scleroderma. J AM ACAD DERMATOL1982;7:541-4. 8. Allansmith MK. Treatment of external diseases with imrnunological properties. Int Ophthalmol Clin 1973;13 (4):193-210. 9. Gordon W. Some diseases involving the eye and the skin. S Afr Med J 1971;45:307-9. 10. Smith CA, Pinals RS. Periorbital edema in systemic lupus erythematosus. Arch Intern Med 1982;142:1711-2. 11. Tuffanelli DL, Dubois EL. Cutaneous manifestations of systemic lupus erythematosus. Arch Dermatol 1964;90: 377-86. 12. Brenner DH, Shock MC. Proptosis secondary to systemic lupus erythematosus. Arch Ophthalmol 1974;91:81-2. 13. Hebra F, Kaposi M. On diseases of the skin including the exanthemata. Tay W, trans. London: The New Sydenham Society, 1875:18. 14. Manschot WA. The eye in collagen diseases. Bibl Ophthalmol 1961;58:1-87. 15. Klauder JV, DeLong P. Lupus erythematosus of the conjunctiva, eyelidsand lid margins. Arch Ophthalmol 1932;7: 856-67. 16. DeLong P, Klauder JV. Lupus erythematosus of the eyelids and conjunctiva. Arch Ophthalmol 1936;16:321-2. 17. Anderson HF, Musgrave DP. Lupus erythematosus of the conjunetiva and lid margin; report of a case. Arch Dermatol Syph 1949;59:247-8. 18. Farkas TG. Discoid lupus erythematosus of the eyelids. Ophthalmol Digest 1973;35(9):21-4. 19. Feiler-Ofry V, Isler Z, Hanau D, et al. Eyelid involvement as the presenting manifestation of discoid lupus erythematosus. J Pediatr Ophthalmol Strabismus 1979;16:395-7. 20. Nowinski T, Bernardina V, Naidoff M, et al. Ocular involvement in lupus erythematosus profundus (panniculitis). Ophthalmology 1982;89:1149-54. 21. Huey C, Jakobiec FA, Iwamoto T, et al. Discoid lupus erythematosus of the eyelids. Ophthalmology 1983;90: 1389-95. 22. Donzis PB, Insler MS, Buntin DM, et al. Discoid lupus erythematosus involving the eyelids. Am J Ophthalmol 1984;98:32-6. 23. Anderson LL, Grimwood RE. Discoid lupus erythematosus manifesting as chronic blepharifis. J Assoc Milit Dermatol 1989;15(2):12-5. 24. Ziv R, Schewach-Millet M, Trau H. Discoid lupus erythe~ matosus of the eyelids [Letter]. J AM ACADDERMATOL 1986;15:112-3.
Journal of the American Academy of Dermatology
Cyran et al. 25. Tosti A, Tosti G, Giovannini A. Discoid lupus erythematosus solely involving the eyelids: report of three cases [Letter]. J AM ACAD DERMATOL 1987;16:1259-60. 26. Sontheimer RD, Maddison PH, Reichlin M, et at. Serologic and HLA associations of subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 1982;97:664-71. 27. Sontheimer RD. Subacute cutaneous lupus erythematosus: a decade's perspective. Med Clin North Am 1989;73:107390. 28. Burnham TK, Fine G. The immunofluorescent "band" test for lupus erythematosus. I. Morphologic variations of the band of localized immunoglobulins at the dermal-epidermal junction in lupus erythematosus. Arch Dermatol t 969; 99:413-20. 29. Tuffanelli DL, Kay D, Fukuyama K. Dermal-epidermal junction in lupus erythematosus. Arch Dermatol 1969;99: 652-62. 30. Ueki H. Hyaline bodies in subepidermal papillae. Immunohistochemical studies in several dermatoses. Arch Dermatol 1969;100:610-7. 3 l. Wallace D J, Dubois EL. Lupus erythematosus. Philadelphia: Lea & Febiger, 1987:294. 32. Tuffanelli DL. Lupus erythematosus pannieulitis (profuudus): clinical and immunologic studies. Arch Dermatol 1971;103:231-42. 33. Ellis FA, Bundik WR. Histology of lupus erythematosus. Arch Dermatot 1954;70:311-24.
34. McCreight WG, Montgomery H. Cutaneous changes in lupus erythematosus: Histopathologic aspects, with special reference to vascular changes. Arch Dermatol 1950;61:111. 35. Marks J, Birkett DA, Shuster S. Capillary permeability in patients with coDagen vascular diseases. Br Med J 1972;1:782-4. 36. Gilje O, O'Leary PA, Baldes EJ. Capillary microscopic examination in skin diseases. Arch Dermatol 1953;68:136-47. 37. Weigand DA, Burgdorf WHC, Gregg LJ. Dermal mucinosis in discoid lupus erythematosus. Arch Dermatol 1981;117:735-8. 38. Van Der Meer-Roosen CH, Maes EPJ, Faber WR. Cutaneous lupus erythematosus and autoimmune thyroiditis. Br J Dermatol 1979;101:91-2. 39. Mulhern LM, Masi AT, Shulrnan LE. Hashimoto's disease: a search for associated disorders in 170 clinically detected cases. Lancet 1966;1:508-11. 40. Miller FW, Moore GF, Weintraub BD, et al. Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus. Arthritis Rheum 1987;30:1124-31. 41. Shirakawa H, Amemiya T, Kasagi K, et al. Hashimoto disease with hyperthyroid ocular signs. Metab Pediatr Ophthalmol 1981;5:213-8.
Cutaneous T-cell lymphoma associated with granular lymphocytic leukemia in its terminal stage A k e m i Seno, M D , a Akiko Okatani, M D , a M a s a t o Miyashita, M D , a N o r i k o Hirano, M D , a Jir6 A r a t a , M D , a N o r i h i r o T e r a m o t o , M D , b T a d a s h i Yoshino, M D , b T a d a a t s u Akagi, M D , b a n d H a r u k o K a t a y a m a , M D e Okayama, Japan A 79-year-old woman had cutaneous T cell lymphoma. After a long clinical course, numerous tumors and an enormous increase in peripheral granular lymphocytes without lymphadenopathy developed suddenly. Surface markers and D N A analysis of the tumor cells from her skin and peripheral blood and electron microscopic examination suggested that granular lymphocytic leukemia had developed in the terminal stage of cutaneous T cell lymphoma. To our knowledge this association has not been reported previously. (J AM ACAD DERMATOL 1992;26:338-42.) C u t a n e o u s T cell l y m p h o m a ( C T C L ) with cutaneous t u m o r s is associated with a m e a n survival of 2.5 years. 1 W e report a patient with C T C L who de-
veloped associated acute leukemia in the terminal stage of her disease.
From the Departmentof Dermatologya and the Second Departmentof Pathology,b Okayama UniversityMedical School, and the Departmerit of Dermatology,Saiseikai Hospital.c Reprint requests: Jir6 Arata, MD, Department of Dermatology, Okayama UniversityMedical School, Shikata-eh6 2-5-1, Okayama 700, Japan. 16/4/28219
A 79-year-old woman was seen in September 1987 because of a tumor on her back of 6 months' duration. She began to have pruritic, erythematous macules with fine scales in 1980. These first appeared on the abdomen and gradually spread to most areas of her body. On physical examination a 3 • 6 cm dumbbell-shaped,
338
CASE R E P O R T
Detroit, Michigan We report two unusual cases of cutaneous lupus erythematosus presenting as dramatic eyelid edema and erythema. Neither patient had evidence of systemic or other significant cutaneous involvement. The eyelid edema and erythema were unilateral in one case and bilateral in the other. Both cases responded to therapy with antimalarial drugs. (J AM ACADDERMATOL 1992;26:334-8.)
Although facial involvement in chronic cutaneous lupus erythematosus ( C C L E ) is common, eyelid involvement as the sole manifestation of C C L E is rare. W e present two cases of eyelid edema and erythema as the sole manifestation of C C L E and review the literature. CASE REPORTS Case 1 A 5 l-year-old white woman had a 3- to 4-month history of asymptomatic left-sided eyelid edema and erythema. She was otherwise well. A prior ophthalmologic examination and plain films of the sinuses revealed no abnormalities. Results of routine laboratory studies were negative. Testing for antinuclear antibodies (ANAs) was positive at a titer of 1:160 in a speclded pattern. A course of sulfacetamide eyedrops had been of no benefit but several brief courses of oral prednisone provided temporary improvement. The patient had two sisters with lupus erythematosus (LE), one of whom died of complications of her disease; the other may have had only cutaneous involvement. Examination revealed marked left eyelid edema and erythema with slight crusting of the upper eyelid (Fig. 1). A repeat test for ANA was positive at 1:140 (HEp-2 cells) in a homogeneous pattern. Anti-double-stranded DNA was negative, anti-Ro (SSA) was positive, and anti-La (SSB), anti-RNP, and anti-Sm were negative. A chest x-ray film was normal and a computed tomographic (CT) scan of the orbit showed only mild soft tissue swelling of the left malar area. Patch testing to the 20 standard antigens of the American Academy of Dermatology From the Department of Dermatology,Henry FordHospital. Reprint requests:Margaret C. Douglass,MD, Departmentof Dermatology,2799W. Grand Blvd.,Detroit, MI 48202. 16/4/3~48 334
(AAD) panel (Allergen Patch Test Kit, Hermal Kurt Herrmann, Reinbeck, Germany) was negative. A skin biopsy specimen showed mild hyperkeratosis, diffuse epidermal atrophy with focal erosion and focal vacuolization of the basal cell layer of the epidermis, and infundibular follicular epithelium with occasional Civatte bodies. The dermis showed edema, telangiectases, and a moderately dense, superficial and deep perivaseular and focally perifollicular lymphohistioeytic infiltrate that contained a few plasma cells (Fig. 2). Direct immunofluorescence showed granular deposition of IgG, IgM, IgA, and C3 along the basement membrane zone (Fig. 3). Quinacrine was started at a dose of 100 mg per day. After 5 weeks there was marked improvement in the eyelid erythema and edema; however, the drug was discontinued because of a generalized drug eruption. Ten months after therapy was discontinued the patient's eyelid edema and erythema remained in remission. Because of her history of thyroid disease, thyroid studies were obtained, which showed a low normal T4, an elevated thyrotropin at twice the upper limit of normal, and markedly elevated thyroid antimicrosomal and antithyroglobulin antibodies at l:1600 and 1:6400, respectively. These values were consistent with a diagnosis of autoimmune thyroiditis, and thyroid replacement therapy was started. Case 2 A 45-year-old white woman had asymptomatic, intermittent left eyelid edema and erythema in August 1988. An ophthalmologist diagnosed "nasolacrimal duct obstruction." A left nasolacrimal stent was placed with no improvement. A C T scan of the orbit revealed only leftsided eyelid edema. Subsequently, a dacryocystorhinostomy and medial and anterior orbit exploration and biopsy were performed. The specimen revealed fibromuscular tissue with a lymphohistiocytic infiltrate. Patch testing to fiberglass and cellulose to which the patient was
Volume 26 Number 2, Part 2 February 1992
CCLE presenting as periorbital edema and erythema 335
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Fig. 1. Patient 1. T,e~teyelkl edema and eryfl~ema, with slight crusting. Fig. 2. Patient 1. LGt eyelid. Diffuse epidermal atrophy, ~oc~lbasal vacuolopathy, dermal edema, and dense peri~ascular ~nd pefifolHcular [ymphohistiocy~ic infiltrate. (• basement m~brane zone. (Fluor~ccin isothiocyanate; • Fig. 4. P~tient 2. Bilater~! eydk] edema and erythema. Fig. 5. Patient2. Leftlowereyelid. Epidermalatrophy, focalbasalvacuolopathy, anddense perivascular and perifollicular lymphohistiocytic infiltrate. (•
"~"
336
Cyran et aL
exposed as a shipping clerk was negative. Several courses of oral prednisone provided temporary improvement but the edema and erythema recurred intermittently. Right eyelid edema and erythema developed approximately 1 year later. Bilateral anterior orbitotomies with excisional biopsies of orbital contents and skin biopsies of both lower eyelids were performed. These revealed lymphohistiocytic infiltration of the adipose tissue and fibromuscular tissue of the orbits and a perivascular and papillary dermal Iymphohistiocytic infiltrate in the eyelid specimens. The patient was referred to the Henry Ford Hospital Departrnent of Dermatology in November 1989. She had bilateral eyelid edema and erythema (Fig. 4). Results of routine laboratory studies were negative. Testing for ANA (HEp-2 cells) was negative as was testing with antibodies to Ro (SSA) and La (SSB). Patch testing to 20 standard antigens and the brown paper wrapping that she used at work was negative. A biopsy specimen from the left lower eyelid showed epidermal atrophy with hydropic degeneration and multiple eosinophilic globules. In the dermis there was a pedvascular and periadnexal iymphohistiocytie infiltrate (Fig. 5). Direct immunofluorescence staining revealed globular fluorescence along the dermoepidermaljunction with IgG, IgM, IgA, and C3. The patient was treated with hydroxychloroquine, 200 rag/ day, and showed mild improvement. Her dose was increased to 400 rag/day after 2 months and prednisone was added at an initial dose of 40 mg/day. After 2 more months the erythema and edema were nearly completely resolved and therapy was discontinued. She has remained in remission for 8 months.
'DISCUSSION Periorbital edema has been reported in patients with systemic lupus erythematosus (SLE). 1~ Tuffanelli and Dubois jt reported a 0.1% incidence of periorbital edema as the presenting manifestation of SLE and an overall incidence of 4.8%. In a review of these articles, it appears that the authors were using the term periorbital edema synonymously with eyelid edema. Unilateral proptosis has also been described in LE, and in one case report it appeared to coincide with the progression of localized cutaneous to systemic disease. 12 In our cases, there was no evidence of systemic involvement or progression to SLE. In their description of the "discoid" form of localized lupus erythematosus (DLE), Hebra and Kaposi 13 included the eyelids as a site of involvement. Several subsequent reports have mentioned the eyelid as a potential site of cutaneous involvement of the lesions of DLE. 7, 8,14 We have found 21 cases in the English-language literature of L E limited to the skin
Journal of the American Academy of Dermatology
with lesions involving, or limited to, the eyelids.15-25 In these case reports, the lesions were variously described as marginal blepharitis, usually with loss of cilia, or as infiltrated plaques, with characteristic "discoid" features of atrophy, scarring, telangiectasia, and follicular plugging. In only two of these case reports, however, did the eyelid findings consist solely of edema. Both patients were A N A negative. In one patient, the edema was bilateral but associated with an additional discoid plaque involving the skin of the supraorbital ridge. 2~ Evidence of lupus panniculitis was also seen. In the other patient it was unilateral and the sole cutaneous finding. 22 In that patient, SSA antibodies were negative, and direct immunofluorescence showed IgG, IgM, complement and fibrin deposition at the DE junction with the presence of cytoid bodies. Our first patient was positive for anti-Ro (SSA) antibody. Although this antibody is present in 30% to 40% of patients with SLE, 2 it is also present in approximately two thirds of patients with subacute cutaneous lupus erythematosus (SCLE). 26 Because her cutaneous eruption was nonscarring, it m a y be appropriate to consider it as a variant of SCLE. However, the eruption did not have the characteristic papulosquamous or annular polyeyclic appearance and the patient lacked any other evidence of systemic disease. In addition, patients with S C L E typically have arthritis or arthralgias, and up to half fulfill at least four of the American R h e u m a t i s m Association's criteria for SLE. 27 We are using the term chronic cutaneous lupus erythematosus to refer to the particular subset of LE into which our patients fall. Their disease is limited to the skin but the lesions lack the features of atrophy, scarring, and follicular plugging associated with the discoid form of cutaneous LE. In our second patient, direct immunofluorescence testing showed deposition of immunoglobulin and complement in a globular pattern. This globular pattern, consisting of ovoid "hyaline" bodies, although not specific for LE, has been described in the subepidermal papillary regions and epidermis in LE.28, 29 The hyaline bodies have been postulated to arise from epidermal cells and basement membrane. 3~ This pattern has also been described in lichen planus, mycosis fungoides, and dermatomyositis. 31 Our second case illustrates the difficulty in making the diagnosis of LE when the disease is limited to the eyelids. In the case reports of LE with eyelid
Volume 26 Number 2, Part 2 February 1992
CCLE presenting as periorbital edema and erythema 337
involvement the average duration until the time of diagnosis was 3 years. The average time until diagnosis in the patients with eyelid erythema and edema only, including our two patients, was 2 years. The appearance of an inflammatory infiltrate in fragments of orbital adipose tissue in our second patient suggests the possibility of lupus panniculitis, which may occur in association with CCLE. 32 Seven of the 21 patients reported with cutaneous LE limited to, or involving, the eyelids were treated with chloroquine (on of these with chloroquine in association with oral corticosteroids) and four with hydroxychloroquine.15-25 All but one of the patients treated with chloroquine improved, as did all of the patients treated with hydroxychloroquine. One patient was treated with intralesional steroids but the clinical response was not indicated. Our two patients responded to quinacrine or hydroxychloroquine. The edema in our patients probably results from the combination of loose areolar connective tissue in the periorbital area and the dermal edema that is a characteristic feature of the cutaneous lesions of LE.33, 34 Marks et al. 35 showed that capillary permeability is increased in inflammatory lesions of patients with collagen vascular diseases, and Gilje et al.36 have shown by capillary microscopy dilated capillaries and arterioles with exudation of serum into the surrounding tissues in erythematous lesions of LE. The presence of dermal mucin, which occurs in discoid LE, may also account for the edematous appearance of the lesions. 37 Our first patient demonstrated the association of autoimmune thyroiditis with CCLE. We know of no other reports of this association. However, SLE occurs in conjunction with other disorders characterized by autoantibody formation including autoimmune thyroiditis. Several reports have estimated the coincidence of these two disorders to be between 0.2% and 4%.38, 39 Miller et al.4~ recently studied 175 patients with SLE and found 45% with an elevated thyrotropin and 10.9% with thyrotropin greater than twice normal. Elevated and antithyroglobulin antibodies were found in 7.1% and 18.4% had elevated antimicrosomal antibodies. They concluded that 44% of these patients had either subclinical or biochemical primary hypothyroidism, which is much higher than the prevalence in the normal population. Although eyelid edema has been described in association with Hashimoto's thyroiditis, 41the characteristic histologic and immunofluorescence find-
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34. McCreight WG, Montgomery H. Cutaneous changes in lupus erythematosus: Histopathologic aspects, with special reference to vascular changes. Arch Dermatol 1950;61:111. 35. Marks J, Birkett DA, Shuster S. Capillary permeability in patients with coDagen vascular diseases. Br Med J 1972;1:782-4. 36. Gilje O, O'Leary PA, Baldes EJ. Capillary microscopic examination in skin diseases. Arch Dermatol 1953;68:136-47. 37. Weigand DA, Burgdorf WHC, Gregg LJ. Dermal mucinosis in discoid lupus erythematosus. Arch Dermatol 1981;117:735-8. 38. Van Der Meer-Roosen CH, Maes EPJ, Faber WR. Cutaneous lupus erythematosus and autoimmune thyroiditis. Br J Dermatol 1979;101:91-2. 39. Mulhern LM, Masi AT, Shulrnan LE. Hashimoto's disease: a search for associated disorders in 170 clinically detected cases. Lancet 1966;1:508-11. 40. Miller FW, Moore GF, Weintraub BD, et al. Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus. Arthritis Rheum 1987;30:1124-31. 41. Shirakawa H, Amemiya T, Kasagi K, et al. Hashimoto disease with hyperthyroid ocular signs. Metab Pediatr Ophthalmol 1981;5:213-8.
Cutaneous T-cell lymphoma associated with granular lymphocytic leukemia in its terminal stage A k e m i Seno, M D , a Akiko Okatani, M D , a M a s a t o Miyashita, M D , a N o r i k o Hirano, M D , a Jir6 A r a t a , M D , a N o r i h i r o T e r a m o t o , M D , b T a d a s h i Yoshino, M D , b T a d a a t s u Akagi, M D , b a n d H a r u k o K a t a y a m a , M D e Okayama, Japan A 79-year-old woman had cutaneous T cell lymphoma. After a long clinical course, numerous tumors and an enormous increase in peripheral granular lymphocytes without lymphadenopathy developed suddenly. Surface markers and D N A analysis of the tumor cells from her skin and peripheral blood and electron microscopic examination suggested that granular lymphocytic leukemia had developed in the terminal stage of cutaneous T cell lymphoma. To our knowledge this association has not been reported previously. (J AM ACAD DERMATOL 1992;26:338-42.) C u t a n e o u s T cell l y m p h o m a ( C T C L ) with cutaneous t u m o r s is associated with a m e a n survival of 2.5 years. 1 W e report a patient with C T C L who de-
veloped associated acute leukemia in the terminal stage of her disease.
From the Departmentof Dermatologya and the Second Departmentof Pathology,b Okayama UniversityMedical School, and the Departmerit of Dermatology,Saiseikai Hospital.c Reprint requests: Jir6 Arata, MD, Department of Dermatology, Okayama UniversityMedical School, Shikata-eh6 2-5-1, Okayama 700, Japan. 16/4/28219
A 79-year-old woman was seen in September 1987 because of a tumor on her back of 6 months' duration. She began to have pruritic, erythematous macules with fine scales in 1980. These first appeared on the abdomen and gradually spread to most areas of her body. On physical examination a 3 • 6 cm dumbbell-shaped,
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