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Subacute cutaneous lupus erythematosus lesions precipitated by griseofulvin
Volume 21 Number 2, Part 2 August 1989
Furosemide-induced simulation of Sweet's syndrome
itated by a medication? One week after treatment with co-trimoxazole, that patient developed plaques of Sweet's syndrome on the arms and back as well as nodules of erythema nodosum on the lower legs. Although unproved, it is believed that immune complexes may be involved in the pathogenesis of Sweet's syndrome. 19 It is conceivable that for this patient, furosemide was involved in such a hypersensitivity reaction. REFERENCES 1. Bigby M, Jick S, Jick H, et al. Drug-induced cutaneous reaction: a report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA 1986;256:3358-63. 2. MacMillan AL. Generalized pustular drug rash. Dermatologica 1973;146:285-91. 3. Su WPD, Lui H-NH. Diagnostic criteria for Sweet's syndrome. Cutis 1986;37:167-74. 4. Storer JS, Nesbitt LT, Galen WK, et al. Sweet's syndrome. Int J Dermatol 1983;22:8-12. 5. Greer KE, Pruitt JL, Bishop GF. Acute febrile neutrophilic dermatosis (Sweet's syndrome). Arch Dermatol 1975;111:1461-3. 6. Burry JN, Lawrence JR. Phototoxic blisters from high furosemide dosage. Br J Dermatol 1976;94:495-9. 7. Kennedy AC, Lyell A. Acquired epidermolysis bullosa due to high-dose furosemide. Br Med J 1976;1:1509-10.
!
I
8. Keczkes K, Farr MJ. Cutaneous bullae and fumsemide in chronic renal failure. Br Med J 1976;2:236. 9. Coles GA, Verrier Jones K. Uraemic bullae. Br Meal J 1976;2:525-6. 10. Heydenreich G, Pindborg T, Schmidt H. Bullous dermatosis among patients with chronic renal failure on high dose furosemide. Acta ivied Scand 1977;202:61-4. 11. Ehringer A, Adam WR, Parkin JD. Bullous haemorrhagic eruption associated with furosemide. Med J Aust 1969;1:768-70. 12. Gibson TP, Blue P. Erythema multiforme and furosemide therapy. JAMA 1970;212:1709. 13. Zugerman C, La Voo EJ. Erythema multiforme caused by oral furosemide. Arch Dermatol 1980;116:518-9. 14. Fellner M J, Katz JM. Occurrence of bullous pemphigoid after furosemide therapy. Arch Dermatol 1976;112: 75-7. 15. Hendricks WM, Ader RS. Furosemide-induced cutaneous necrotizing vacuIitis. Arch Dermatol 1977;113:375. 16. Guin JD. Bullous hemorrhagic eruption: a drug-induced disease. Curls 1980;25:534-6. 17. Harber LC, Bickers DP. Porphyria and pseudoporphyria. J Invest Dermatol 1984;82:207-9. 18. Goldsman CI, Taylor JS. Porphyria cutanea tarda and bullous dermatoses associated with chronic renal failure: a review. Cleve Clin Q 1983;50:151-61. 19. Callen JP. Acute febrile neutrophilic dermatosis (Sweet's syndrome) and the related conditions of "bowel bypass" syndrome and bullous pyoderma gangrenosum. Dermatol Clin 1985;3:153-63.
I
Subacute cutaneous lupus erythematosus lesions precipitated by griseofulvin Sachiko Miyagawa, MD, Toshie Okuchi, MD, Yuko Shiomi, MD, and Kuniki Sakamoto, MD Nara, Japan Skin eruptions with features of subacute cutaneous lupus erythematosus occurred in a patient with dermatomyositis who was taking griseofulvin. The patient had antibodies against SSA/Ro and SSB/La antigens. Skin rashes disappearedafter discontinuation of griseofulvin and recurred on challenge with the drug. These findings support previous studies that the photoactive drug may be synergistic with anti-SSA/Ro antibody to produce lesions of subacute cutaneous lupus erythematosus. (J AM ACAO DERMATOL 1989;21:343-6.) Griseofulvin is a known photosensitizer, and exacerbation of systemic lupus erythematosus or From the Department of Dermatology,Nara Medical University. Reprint requests: Saehiko Miyagawa, MD, Department of Dermatology, Nara Medical University, Nara 634, Japan.
unmasking of lupus diathesis has been reported after its oral administration.~-4 We report a case of systemic lupus erythematosus in which griseofulvin was associated with eruptions with clinical and laboratory features similar to those of subacute cutaneous lupus erythematosus. 343
344
Journal of the American Academy of Dermatology
Miyagawa et al.
CASE REPORT
In May 1984 a 35-year old woman with a 10-month history of dermatomyositis was admitted to the hospital because of malaise, fever, and rash. The symptoms had begun a few days before admission, after 2 weeks of continuous oral therapy with griseofulvin, 375 mg/day, for onychomycosis of the fingernails and toenails. The diagnosis of dermatomyositis had been made on the basis of proximal muscle weakness, diffuse erythematous skin rash on the face and shoulders, findings on biopsy of deltoid muscle specimens and electromyography, and elevated muscle enzyme levels. The patient had been treated with maintenance doses of prednisolone, 20 rag/day, since March 1984. Her serum samples contained antinuclear antibodies by indirect immunofluorescence with the use of HEp-2 cell preparation as a substrate. Antinuclear antibody profiles for U1RNP, Sin, and DNA were negative. Anti-SSA/Ro and SSB/ La antibodies were found to be positive. Physical examination of the patient demonstrated a new outbreak of erythematous-papulosquamous lesions on the face, neck, trunk (Fig. 1), and external surface of the arms. Her body temperature was 38.4 ~ C. Histologic examination of a biopsy specimen taken from a lesion on the upper portion of the back revealed hyperkeratosis, keratotic plugging, epidermal atrophy, liquefaction degeneration of the basal cell layer, and dermal perivascular lymphohistiocytic infiltrate (Fig. 2). Immunoenzymestaining (Fig. 3) showed IgG deposition at the dermoepidermal junction. Deposition of other immunoglobulins and components of complement was not found. Positive laboratory findings included an elevated erythrocyte sedimentation rate of 36 mm/hr, a test for rheumatoid factor, and antinuclear antibodies at a tiler of l:160 on HEp-2 cells. Anti-SSA/Ro and SSB/La antibodies were positive at titers of 1:80 and 1:20, respectively, by conventional immunodiffusion. Other laboratory studies, which showed either negative or normal findings, included complete blood cell and differential counts, urinalysis, serum protein, serum immunoelectrophoresis, lupus erythematosus cell test, total hemolytic complement, liver function tests, and anti-DNA antibody test. Laboratory signs of exacerbation of dermatomyositis were not observed. Human lymphocyte antigen (HLA) genotypes were A9, B40, Cw3, and DR5. HLA antigens B8 and DR3, which show strong association with subacute cutaneous lupus erythematosus and myositis, s* were not found. Griseofulvin was discontinued. Under treatment with prednisolone, 60 rag/day, the skin lesions disappeared and the acute symptoms subsided. Prednisolone was gradually tapered to a maintenance dose of 20 rag/ day.
Five months after resolution of the initial rash, the patient was again given griseofulvin, 375 mg/day. On the third day, she felt unwell, and on the fourth and fifth days she had dizziness and headache. The rash recurred by the fourteenth day on the face, neck, arms, and upper portion of the trunk. Exacerbation of dermatomyositis was not observed. The skin lesions resolved by discontinuation of griseofulvin within 2 weeks. The patient was discharged from the hospital in May 1985. She has been well since and receiving the maintenance dose of prednisolone for dermatomyositis. Circulating anti-SSA/Ro and SSB/La antibody titers showed only a tube dilution test difference of 1:2 during the observation period. DISCUSSION Subacute cutaneous lupus erythematosus is a subset of lupus erythematosus that is characterized by distinct immunologic abnormalities and some systemic features. 5,9 Skin lesions usually are widespread and nonscarring, with associated scaling on face, neck, upper portions of the chest and back, shoulders, and extensor areas, which can last for weeks to months. The histopathologic characteristics of subacute cutaneous lupus erythematosus show changes consistent with, although more subtie than, those of discoid lupus erythematosus. The epidermis is mildly atrophic, and hyperkeratosis is scant. There is liquefaction degeneration of the dermoepidermal junction and a mild lymphohistiocytic perivascular infiltrate. The demonstration of immunoreactants at the dermoepidermal junction in subacute cutaneous lupus erythematosus is less frequently positive than it is with systemic lupus erythematosus and may be negative in up to 40% of patients. Anti-SSA/Ro antibodies are seen in as many as 80% of these patients, whereas antiS S B / L a antibodies are seen less frequently. Our patient had skin lesions that were papulosquamous with fine scaling, similar to those of subacute cutaneous lupus erythematosus. Serologic, histopathologic, and immunohistopathologic findings were compatible with those of subacute cutaneous lupus erythematosus. The clinical resolution of the skin lesions after discontinuation of griseofulvin and recurrence on challenge with the drug strongly implies that this drug was associated with the clinical and histologic epidermal changes in the patient. Subacute cutaneous lupus erythematosus lesions developed on challenge with griseofulvin despite the patient's careful avoidance of direct
Volume 21 Number 2, Part 2 August 1989
SCLE lesiorL~precipitated by griseofidvin 345
9.
2"
"
,.
"
.
Fig. 1. Paputosquamous subacute cutaneous lupus erythematosus lesions on the back. Fig. 2. Photomicrograph of a skin biopsy specimen showing hyperkeratosis, epidermal atrophy, liquefaction degeneration of the basal layer, and inflammatory infiltrate in the dermis. (x200.) Fig. 3. Photomicrograph of linear depositionof IgG at the epidermal basement membrane zone observed by the peroxidase-antiperoxidasemethod. (Xl00.)
sun exposure during hospitalization. Thus some effect in addition to photosensitization may be exerted by griseofulvin. There is strong indirect evidence that antibodies to SSA/Ro are pathologicalIy involved in the development of the epidermal changes in subacute cutaneous lupus erythematosus. Antibodies to SSA/Ro bind to the surface of cultured keratinocytes in vitro, and this binding is accentuated by previous exposure of the keratinocytes to ultraviolet light ~0or treatment with estrogen.t1 Similar binding
of anti-SSA/Ro antibodies to the surface of keratinocytes in grafts of human skin on nude mice has been observed after intravenous injection of antiSSA/Ro antibodies into mice; again, ultraviolet light accentuates this phenomenonJ 2 The expression of SSA/Ro antigen in human keratinocytes possibly is associated with ceU proliferation. ~ The mechanism by which anti-SSA/Ro antibodies induce keratinocyte damage is not known, but there is considerable evidence that anti-SSA/Ro antibodies may induce antibody-dependent cellular
346
Journal of the American Academy of Dermatology
Miyagawa et al.
cytotoxicity of cells bearing the S S A / R o gen.14' is
anti-
Although t h e precise m e c h a n i s m is currently unknown, griseofulvin m a y b e involved in enhancing this cytotoxic reaction. T h e possibility that the effect of griseofulvin is directly involved in antib o d y production is unlikely, because the skin disease subsides on discontinuation of the drug, whereas a n t i - S S A / R o antibody titers remain unchanged. O u r findings, t o g e t h e r with those o f a previous report of subacute c u t a n e o u s lupus erythematosus caused by hydrochlorothiazide, t6 indicate that photoactive drugs are likely to be synergistic with a n t i - S S A / R o antibodies in producing cutaneous lesions of s u b a c u t e cutaneous lupus erythematosus.
7. 8.
9.
10.
11.
12.
REFERENCES
1. Alexander S. Lupus erythematosus in two patients after griseofulvin treatment of Trichophyton rubrum infection. Br J Dermatol 1962;74:72-4. 2. Anderson WA, Torre D. Griseofnlvin and lupus erythematosus. J Meal Soc NJ 1966;63:161-2. 3. Watsky MS, Linfield Y. Lupus erythematosus exacerbated by griseofulvin. Cutis 1976;17:361-3. 4. Madhok R, Zoma A, Capell H. Fatal exacerbation of systemic lupus erythematosus after treatment with griseofulvin. Br Med J 1985;291:249-50. 5. Sontheimer RD, Maddison PJ, Reichlin M, Jordon E, Stastny P, Gilliam JN. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 1982;97:66471. 6. Sontheimer RD, Stastny P, Gilliam JN. Human histo-
13. 14.
15. 16.
compatibility antigen associations in subacute cutaneouos lupus erythematosus. J Clin Invest 1981;67:312-6. Behan WMH, Behan PO, Dick HA. HLA-B8 in polymyositis. N Engl J Med 1978;298:1260-1. Sasazuki T, McDevitt HO, Grumet FC. The association between genes in the major histocompatibility complex and disease susceptibility. Ann Rev Med 1977;28:42552. Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 1979;115:1409-15. LeFeber WP, Norris DA, Ryan SR, et al. Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest 1984;74:1545-51. Furukawa F, Lyons B, Lee LA, Norris DA. Estradiol enhances Ro antigen expression on cultured human keratinocyte cell membranes [Abstract]. Clin Res 1987; 35:388. Lee LA, Weston WL, Krueger GO, et al. An animal model of antibody binding in cutaneous lupus. Arthritis Rheum 1986;29:782-8. Miyagawa S, Okada N, Inagaki Y, et al. SSA/Ro antigen expressionin simian virus 40-transformed human keratinocytes. J Invest Dermatol 1988;90:342-5. Norris DA, Ryan SR, Fritz KA, et al. The role of RNP, Sin, and SS-A/Ro-speeific antisera from patients with lupus erythematosus in inducing antibody-dependent cellular cytotoxicity (ADCC) of targets coated with nonhistone nuclear antigens. Clin Immunol Immunopathol 1984;31:311-20. Norris DA, Lee LA. Antibody-dependent cellular cytotoxicity and skin disease. J Invest Dermatol (suppl) 1985;85:165-75. Reed BR, Huff JL, Jones SK, Orton PW, Lee LA, Norris DA. Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. Ann Intern Med 1985;103:49-51.
Furosemide-induced simulation of Sweet's syndrome
itated by a medication? One week after treatment with co-trimoxazole, that patient developed plaques of Sweet's syndrome on the arms and back as well as nodules of erythema nodosum on the lower legs. Although unproved, it is believed that immune complexes may be involved in the pathogenesis of Sweet's syndrome. 19 It is conceivable that for this patient, furosemide was involved in such a hypersensitivity reaction. REFERENCES 1. Bigby M, Jick S, Jick H, et al. Drug-induced cutaneous reaction: a report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA 1986;256:3358-63. 2. MacMillan AL. Generalized pustular drug rash. Dermatologica 1973;146:285-91. 3. Su WPD, Lui H-NH. Diagnostic criteria for Sweet's syndrome. Cutis 1986;37:167-74. 4. Storer JS, Nesbitt LT, Galen WK, et al. Sweet's syndrome. Int J Dermatol 1983;22:8-12. 5. Greer KE, Pruitt JL, Bishop GF. Acute febrile neutrophilic dermatosis (Sweet's syndrome). Arch Dermatol 1975;111:1461-3. 6. Burry JN, Lawrence JR. Phototoxic blisters from high furosemide dosage. Br J Dermatol 1976;94:495-9. 7. Kennedy AC, Lyell A. Acquired epidermolysis bullosa due to high-dose furosemide. Br Med J 1976;1:1509-10.
!
I
8. Keczkes K, Farr MJ. Cutaneous bullae and fumsemide in chronic renal failure. Br Med J 1976;2:236. 9. Coles GA, Verrier Jones K. Uraemic bullae. Br Meal J 1976;2:525-6. 10. Heydenreich G, Pindborg T, Schmidt H. Bullous dermatosis among patients with chronic renal failure on high dose furosemide. Acta ivied Scand 1977;202:61-4. 11. Ehringer A, Adam WR, Parkin JD. Bullous haemorrhagic eruption associated with furosemide. Med J Aust 1969;1:768-70. 12. Gibson TP, Blue P. Erythema multiforme and furosemide therapy. JAMA 1970;212:1709. 13. Zugerman C, La Voo EJ. Erythema multiforme caused by oral furosemide. Arch Dermatol 1980;116:518-9. 14. Fellner M J, Katz JM. Occurrence of bullous pemphigoid after furosemide therapy. Arch Dermatol 1976;112: 75-7. 15. Hendricks WM, Ader RS. Furosemide-induced cutaneous necrotizing vacuIitis. Arch Dermatol 1977;113:375. 16. Guin JD. Bullous hemorrhagic eruption: a drug-induced disease. Curls 1980;25:534-6. 17. Harber LC, Bickers DP. Porphyria and pseudoporphyria. J Invest Dermatol 1984;82:207-9. 18. Goldsman CI, Taylor JS. Porphyria cutanea tarda and bullous dermatoses associated with chronic renal failure: a review. Cleve Clin Q 1983;50:151-61. 19. Callen JP. Acute febrile neutrophilic dermatosis (Sweet's syndrome) and the related conditions of "bowel bypass" syndrome and bullous pyoderma gangrenosum. Dermatol Clin 1985;3:153-63.
I
Subacute cutaneous lupus erythematosus lesions precipitated by griseofulvin Sachiko Miyagawa, MD, Toshie Okuchi, MD, Yuko Shiomi, MD, and Kuniki Sakamoto, MD Nara, Japan Skin eruptions with features of subacute cutaneous lupus erythematosus occurred in a patient with dermatomyositis who was taking griseofulvin. The patient had antibodies against SSA/Ro and SSB/La antigens. Skin rashes disappearedafter discontinuation of griseofulvin and recurred on challenge with the drug. These findings support previous studies that the photoactive drug may be synergistic with anti-SSA/Ro antibody to produce lesions of subacute cutaneous lupus erythematosus. (J AM ACAO DERMATOL 1989;21:343-6.) Griseofulvin is a known photosensitizer, and exacerbation of systemic lupus erythematosus or From the Department of Dermatology,Nara Medical University. Reprint requests: Saehiko Miyagawa, MD, Department of Dermatology, Nara Medical University, Nara 634, Japan.
unmasking of lupus diathesis has been reported after its oral administration.~-4 We report a case of systemic lupus erythematosus in which griseofulvin was associated with eruptions with clinical and laboratory features similar to those of subacute cutaneous lupus erythematosus. 343
344
Journal of the American Academy of Dermatology
Miyagawa et al.
CASE REPORT
In May 1984 a 35-year old woman with a 10-month history of dermatomyositis was admitted to the hospital because of malaise, fever, and rash. The symptoms had begun a few days before admission, after 2 weeks of continuous oral therapy with griseofulvin, 375 mg/day, for onychomycosis of the fingernails and toenails. The diagnosis of dermatomyositis had been made on the basis of proximal muscle weakness, diffuse erythematous skin rash on the face and shoulders, findings on biopsy of deltoid muscle specimens and electromyography, and elevated muscle enzyme levels. The patient had been treated with maintenance doses of prednisolone, 20 rag/day, since March 1984. Her serum samples contained antinuclear antibodies by indirect immunofluorescence with the use of HEp-2 cell preparation as a substrate. Antinuclear antibody profiles for U1RNP, Sin, and DNA were negative. Anti-SSA/Ro and SSB/ La antibodies were found to be positive. Physical examination of the patient demonstrated a new outbreak of erythematous-papulosquamous lesions on the face, neck, trunk (Fig. 1), and external surface of the arms. Her body temperature was 38.4 ~ C. Histologic examination of a biopsy specimen taken from a lesion on the upper portion of the back revealed hyperkeratosis, keratotic plugging, epidermal atrophy, liquefaction degeneration of the basal cell layer, and dermal perivascular lymphohistiocytic infiltrate (Fig. 2). Immunoenzymestaining (Fig. 3) showed IgG deposition at the dermoepidermal junction. Deposition of other immunoglobulins and components of complement was not found. Positive laboratory findings included an elevated erythrocyte sedimentation rate of 36 mm/hr, a test for rheumatoid factor, and antinuclear antibodies at a tiler of l:160 on HEp-2 cells. Anti-SSA/Ro and SSB/La antibodies were positive at titers of 1:80 and 1:20, respectively, by conventional immunodiffusion. Other laboratory studies, which showed either negative or normal findings, included complete blood cell and differential counts, urinalysis, serum protein, serum immunoelectrophoresis, lupus erythematosus cell test, total hemolytic complement, liver function tests, and anti-DNA antibody test. Laboratory signs of exacerbation of dermatomyositis were not observed. Human lymphocyte antigen (HLA) genotypes were A9, B40, Cw3, and DR5. HLA antigens B8 and DR3, which show strong association with subacute cutaneous lupus erythematosus and myositis, s* were not found. Griseofulvin was discontinued. Under treatment with prednisolone, 60 rag/day, the skin lesions disappeared and the acute symptoms subsided. Prednisolone was gradually tapered to a maintenance dose of 20 rag/ day.
Five months after resolution of the initial rash, the patient was again given griseofulvin, 375 mg/day. On the third day, she felt unwell, and on the fourth and fifth days she had dizziness and headache. The rash recurred by the fourteenth day on the face, neck, arms, and upper portion of the trunk. Exacerbation of dermatomyositis was not observed. The skin lesions resolved by discontinuation of griseofulvin within 2 weeks. The patient was discharged from the hospital in May 1985. She has been well since and receiving the maintenance dose of prednisolone for dermatomyositis. Circulating anti-SSA/Ro and SSB/La antibody titers showed only a tube dilution test difference of 1:2 during the observation period. DISCUSSION Subacute cutaneous lupus erythematosus is a subset of lupus erythematosus that is characterized by distinct immunologic abnormalities and some systemic features. 5,9 Skin lesions usually are widespread and nonscarring, with associated scaling on face, neck, upper portions of the chest and back, shoulders, and extensor areas, which can last for weeks to months. The histopathologic characteristics of subacute cutaneous lupus erythematosus show changes consistent with, although more subtie than, those of discoid lupus erythematosus. The epidermis is mildly atrophic, and hyperkeratosis is scant. There is liquefaction degeneration of the dermoepidermal junction and a mild lymphohistiocytic perivascular infiltrate. The demonstration of immunoreactants at the dermoepidermal junction in subacute cutaneous lupus erythematosus is less frequently positive than it is with systemic lupus erythematosus and may be negative in up to 40% of patients. Anti-SSA/Ro antibodies are seen in as many as 80% of these patients, whereas antiS S B / L a antibodies are seen less frequently. Our patient had skin lesions that were papulosquamous with fine scaling, similar to those of subacute cutaneous lupus erythematosus. Serologic, histopathologic, and immunohistopathologic findings were compatible with those of subacute cutaneous lupus erythematosus. The clinical resolution of the skin lesions after discontinuation of griseofulvin and recurrence on challenge with the drug strongly implies that this drug was associated with the clinical and histologic epidermal changes in the patient. Subacute cutaneous lupus erythematosus lesions developed on challenge with griseofulvin despite the patient's careful avoidance of direct
Volume 21 Number 2, Part 2 August 1989
SCLE lesiorL~precipitated by griseofidvin 345
9.
2"
"
,.
"
.
Fig. 1. Paputosquamous subacute cutaneous lupus erythematosus lesions on the back. Fig. 2. Photomicrograph of a skin biopsy specimen showing hyperkeratosis, epidermal atrophy, liquefaction degeneration of the basal layer, and inflammatory infiltrate in the dermis. (x200.) Fig. 3. Photomicrograph of linear depositionof IgG at the epidermal basement membrane zone observed by the peroxidase-antiperoxidasemethod. (Xl00.)
sun exposure during hospitalization. Thus some effect in addition to photosensitization may be exerted by griseofulvin. There is strong indirect evidence that antibodies to SSA/Ro are pathologicalIy involved in the development of the epidermal changes in subacute cutaneous lupus erythematosus. Antibodies to SSA/Ro bind to the surface of cultured keratinocytes in vitro, and this binding is accentuated by previous exposure of the keratinocytes to ultraviolet light ~0or treatment with estrogen.t1 Similar binding
of anti-SSA/Ro antibodies to the surface of keratinocytes in grafts of human skin on nude mice has been observed after intravenous injection of antiSSA/Ro antibodies into mice; again, ultraviolet light accentuates this phenomenonJ 2 The expression of SSA/Ro antigen in human keratinocytes possibly is associated with ceU proliferation. ~ The mechanism by which anti-SSA/Ro antibodies induce keratinocyte damage is not known, but there is considerable evidence that anti-SSA/Ro antibodies may induce antibody-dependent cellular
346
Journal of the American Academy of Dermatology
Miyagawa et al.
cytotoxicity of cells bearing the S S A / R o gen.14' is
anti-
Although t h e precise m e c h a n i s m is currently unknown, griseofulvin m a y b e involved in enhancing this cytotoxic reaction. T h e possibility that the effect of griseofulvin is directly involved in antib o d y production is unlikely, because the skin disease subsides on discontinuation of the drug, whereas a n t i - S S A / R o antibody titers remain unchanged. O u r findings, t o g e t h e r with those o f a previous report of subacute c u t a n e o u s lupus erythematosus caused by hydrochlorothiazide, t6 indicate that photoactive drugs are likely to be synergistic with a n t i - S S A / R o antibodies in producing cutaneous lesions of s u b a c u t e cutaneous lupus erythematosus.
7. 8.
9.
10.
11.
12.
REFERENCES
1. Alexander S. Lupus erythematosus in two patients after griseofulvin treatment of Trichophyton rubrum infection. Br J Dermatol 1962;74:72-4. 2. Anderson WA, Torre D. Griseofnlvin and lupus erythematosus. J Meal Soc NJ 1966;63:161-2. 3. Watsky MS, Linfield Y. Lupus erythematosus exacerbated by griseofulvin. Cutis 1976;17:361-3. 4. Madhok R, Zoma A, Capell H. Fatal exacerbation of systemic lupus erythematosus after treatment with griseofulvin. Br Med J 1985;291:249-50. 5. Sontheimer RD, Maddison PJ, Reichlin M, Jordon E, Stastny P, Gilliam JN. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 1982;97:66471. 6. Sontheimer RD, Stastny P, Gilliam JN. Human histo-
13. 14.
15. 16.
compatibility antigen associations in subacute cutaneouos lupus erythematosus. J Clin Invest 1981;67:312-6. Behan WMH, Behan PO, Dick HA. HLA-B8 in polymyositis. N Engl J Med 1978;298:1260-1. Sasazuki T, McDevitt HO, Grumet FC. The association between genes in the major histocompatibility complex and disease susceptibility. Ann Rev Med 1977;28:42552. Sontheimer RD, Thomas JR, Gilliam JN. Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 1979;115:1409-15. LeFeber WP, Norris DA, Ryan SR, et al. Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest 1984;74:1545-51. Furukawa F, Lyons B, Lee LA, Norris DA. Estradiol enhances Ro antigen expression on cultured human keratinocyte cell membranes [Abstract]. Clin Res 1987; 35:388. Lee LA, Weston WL, Krueger GO, et al. An animal model of antibody binding in cutaneous lupus. Arthritis Rheum 1986;29:782-8. Miyagawa S, Okada N, Inagaki Y, et al. SSA/Ro antigen expressionin simian virus 40-transformed human keratinocytes. J Invest Dermatol 1988;90:342-5. Norris DA, Ryan SR, Fritz KA, et al. The role of RNP, Sin, and SS-A/Ro-speeific antisera from patients with lupus erythematosus in inducing antibody-dependent cellular cytotoxicity (ADCC) of targets coated with nonhistone nuclear antigens. Clin Immunol Immunopathol 1984;31:311-20. Norris DA, Lee LA. Antibody-dependent cellular cytotoxicity and skin disease. J Invest Dermatol (suppl) 1985;85:165-75. Reed BR, Huff JL, Jones SK, Orton PW, Lee LA, Norris DA. Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. Ann Intern Med 1985;103:49-51.