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Subacute cutaneous lupus erythematosus associated with breast carcinoma
Subacute cutaneous lupus erythematosus associated with breast carcinoma M. S c h e w a c h - M i l l e t , M . D . , D. Shpiro, M . D . , R. Ziv, M . D . , and H. Trau, M . D . Tel Hashomer and Tel Aviv, Israel A case of subacute cutaneous lupus erythematosus associated with breast carcinoma is presented. The patient had not been aware of her malignant disease and had consulted us after her dermatosis developed. To date only one case of subacute cutaneous lupus erythematosus associated with malignancy has been described in the literature. The relationship between a derrnatosis and a malignant internal disease is discussed. (J AM ACAD DERMATOL 1988;19:406-8.)
In 1979 S o n t h e i m e r and Gillian' first described the entity k n o w n as subacute cutaneous lupus erythematosus. This subset o f lupus erythematosus is characterized by a benign course, a special type o f photodermatitis, and laboratory and immunologic changes different f r o m those found in systemic lupus erythematosus. Although 30% to 40% o f the patients have a negative antinuclear antibody reaction and a negative immunofluorescence test result, in 60% o f the cases R o / S S A antibody is present. The purpose o f this report is to suggest the possible association between subacute cutaneous lupus e r y t h e m a t o s u s and malignancy. CASE R E P O R T A 67-year-old married woman with two children was referred to the department of dermatology at the Chaim Sheba Medical Center, Tel Hashomer, because of slowly migrating skin lesions of 6 months' duration. Her past medical history was unremarkable except for hypertension, which was controlled by beta blockers. Physical examination revealed that the patient's general condition was good. Her temperature was normal, From the Department of Dermatology, The Chaim Sheba Medical Center, Tel Hashomer, and the Saekler School of Medicine, Ramat Aviv, Tel Aviv. Reprint requests to: Dr. M. Schewach-Millet, Department of Dermatology, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
406
pulse rate was regular, and blood pressure was 150/85 mm Hg. The lungs were clear on percussion and auscultation. Except for one lymph node in the left axilla, neither lymphadenopathy or hepatomegaly was noted. The skin had a nonitchy, slightly scaly, erythematous eruption composed of papules and plaques arranged in rings and arcs, with an elevated border distributed on the face, upper part of the back, and upper extremities (Figs. 1 and 2). The skin biopsy specimens from the chest and back showed diagnostic features of lupus erythematosus. Results of the routine laboratory tests, including hemogram, urinalysis, liver function tests, and protein, sugar, electrolyte, and urea determinations, were within normal limits. Reaction to antinuclear antibody was negative, and results of Coombs', complement latex, and VDRL tests were normal. Human lymphocyte antigen typing was not specific. An anti-Ro-antibody test showed positive results, whereas direct immunofluorescence studies from involved and uninvolved skin and the indirect immunofluorescence test showed negative results. X-ray examination of the lungs and computed tomography of the chest disclosed some foci interpreted as metastases. Ultrasound examination of the abdomen, liver, and spleen and results of bone scan were normal. Neurologic, ophthalmologic, and gynecologic examinations also showed no abnormalities. Mammography revealed a mass in the left breast, and the biopsy specimen confirmed the diagnosis of adenocarcinoma. Because of the high estrogen receptor concentration of the tumor, hormonal therapy was started with a daily dose
Volume 19 Number 2, Part 2 Auf,ust 1988
Subacute cutaneous L E and breast cancer
407
Fig. 1. Plaques arranged in rings and arcs on the chest.
Fig. 2. Annular lesions on the back similar to those on the chest.
of 20 mg tamoxifen. After 6 months of this therapy, complete clearing of the skin lesions was observed, the patient's general condition improved, and a partial regression of the tumor and of the metastases was noted. A few months later the patient gained weight and experienced drowsiness, constipation, and hair loss. The diagnosis of primary hypothyroidism was confirmed by thyroxin (0.9 I~g/dl) tests and high levels of thyroid-stimulating hormone. Although thyroid microsomal antibodies with a titer of 1:2500 were present, there were no thyroid globulin antibodies. The patient was treated with eltroxine, which improved her condition.
tosis occurs before tumor development. However, in practice it is often difficult to ascertain which disease comes first, and therefore this criterion is not always helpful. 2. Both the dermatosis and the tumor should follow a parallel course. This means that if the tumor is removed, the dermatosis clears, conversely, if the tumor recurs, the dermatosis relapses. The parallelism is not difficult to prove when the tumor is removed surgically, but with chemotherapy or hormonal therapy the medication may have nonspecific effects that could suppress the dermatosis without any relation to the tumor. Therefore this criterion is not altogether helpful either. The concept of a paraneoplastic syndrome becomes important only if the skin manifestations help in the recognition of an underlying malignancy. Whether subacute cutaneous lupus erythematosus meets McLean's two criteria is difficult to ascertain. To the best of our knowledge, in 1986 Kuhn and Kaufmann 6 described the only case of this disease associated with malignancy. Their 68-year-old patient suffered from subacute cutaneous lupus erythematosus concomitant with gastric carcinoma. Successful surgery of the tumor resulted in healing of the skin lesions. Our patient, who had subacute cutaneous lupus erythematosus and breast carcinoma, was unaware of her malignant disease and had consulted us only after her dermatosis developed. At this point she already had lung metastases. The hypothyroidism that de-
DISCUSSION It is not uncommon that skin manifestations are the first signs of various types of malignancies, and they often appear before clinical or laboratory findings are available. 2 For many years the concurrence of autoimmune disease, such as systemic lupus erythematosus, with malignancy has been recognized with increased frequency) '4 The reason for this association is obscure, and the question remains whether it constitutes a paraneoplastic syndrome. McLean 5 presents a review of Curth's criteria for the relationship between dermatosis and a malignant internal disease. He narrowed the definition of paraneoplastic syndrome to two essential criteria: 1. The dermatosis must appear after the development of the malignant tumor and cannot be considered a paraneoplastic syndrome if the derma-
Journal of the American Academy of Dermatology
408 S c h e w a c h - M i l l e t et al.
veloped could be interpreted as an additional manifestation of her immunodeficiency. When there is an association between autoimmune and neoplastic disease, the autoimmune disease can precede, coexist, or follow the diagnosis of malignancy. Several explanations have been given for these sequences. 7's'9 When the tumor comes first, the autoimmune phenomenon may be caused by the host's attempt at recognition and suppression of microfoci of tumor. When the autoimmune disease precedes the malignancy, the deficient immune surveillance may be responsible for the development of the tumor. A third possibility is that the autoimmune phenomenon and malignancy are two independent diseases to which the patient is predisposed by the same immunosuppressive factors. In our case, although the first clinical manifestation was the slcin eruption, it was obvious that the patient's breast cancer had been present for some time because she already had pulmonary metastases. The dermatosis disappeared 6 months after therapy was begun, at which time regression of the tumor mass and metastases was noted. This progression would satisfy McLean's second criterion for paraneoplastic disease if it were certain that the hormonal treatment had no direct effect on the dermatosis and that the improvement of the
skin was a consequence of the tumor regression only. We hope that our interesting case will help alert the clinician to the possibility that subacute cutaneous lupus erythematosus can be associated with malignant disease. REFERENCES 1. Sontheimer RD, Gillian IJR. Subacute cutaneous lupus erythematous: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 1979;115:1409-15. 2. Skolnick M, Mainman ER. Erythema gyratum repens with metastatic adenocarcinoma. Arch Dermatol 1975; I i 1:227-9. 3. Chuong JJH, Livstone EM, Barwick KW. Systemic lupus erythematosus and gastric carcinoma: a report of two cases and a critical review of the literature. Am J Gastroenterol 1982;77:611-3. 4. Blanc D, Kienzler JL. Lupus erythematosus gyratus repens: report of a case associated with a lung carcinoma. Clin Exp Dermatol 1982;7:129-34. 5. McLean DJ. Cutaneous paraplastic syndromes. Arch Dcrmatol 1986; ! 22:765-7. 6. Kuhn A, Kaufmann I. Subacute cutaneous lupus erythematosus as a paraneoplastic syndrome. Z Hautkr 1986; 61:581-3. 7. Efremidis A, Eiser AR, Grishman E, Rosenberg V. Hodgkin's lymphoma in an adolescent with systemic lupus erythematosus. Cancer 1984;53:142-6. 8. Milligan DW, Chang JG. Systemic lupus erythematosus and lymphoma. Acta Haematol 1980;64:109-10. 9. Agudelo C, Schumacher HR, Glick JH, Molena J. NonHodgkin's lymphoma in systemic lupus erythematosus. Rheumatology 1984;8:69-78.
In 1979 S o n t h e i m e r and Gillian' first described the entity k n o w n as subacute cutaneous lupus erythematosus. This subset o f lupus erythematosus is characterized by a benign course, a special type o f photodermatitis, and laboratory and immunologic changes different f r o m those found in systemic lupus erythematosus. Although 30% to 40% o f the patients have a negative antinuclear antibody reaction and a negative immunofluorescence test result, in 60% o f the cases R o / S S A antibody is present. The purpose o f this report is to suggest the possible association between subacute cutaneous lupus e r y t h e m a t o s u s and malignancy. CASE R E P O R T A 67-year-old married woman with two children was referred to the department of dermatology at the Chaim Sheba Medical Center, Tel Hashomer, because of slowly migrating skin lesions of 6 months' duration. Her past medical history was unremarkable except for hypertension, which was controlled by beta blockers. Physical examination revealed that the patient's general condition was good. Her temperature was normal, From the Department of Dermatology, The Chaim Sheba Medical Center, Tel Hashomer, and the Saekler School of Medicine, Ramat Aviv, Tel Aviv. Reprint requests to: Dr. M. Schewach-Millet, Department of Dermatology, The Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
406
pulse rate was regular, and blood pressure was 150/85 mm Hg. The lungs were clear on percussion and auscultation. Except for one lymph node in the left axilla, neither lymphadenopathy or hepatomegaly was noted. The skin had a nonitchy, slightly scaly, erythematous eruption composed of papules and plaques arranged in rings and arcs, with an elevated border distributed on the face, upper part of the back, and upper extremities (Figs. 1 and 2). The skin biopsy specimens from the chest and back showed diagnostic features of lupus erythematosus. Results of the routine laboratory tests, including hemogram, urinalysis, liver function tests, and protein, sugar, electrolyte, and urea determinations, were within normal limits. Reaction to antinuclear antibody was negative, and results of Coombs', complement latex, and VDRL tests were normal. Human lymphocyte antigen typing was not specific. An anti-Ro-antibody test showed positive results, whereas direct immunofluorescence studies from involved and uninvolved skin and the indirect immunofluorescence test showed negative results. X-ray examination of the lungs and computed tomography of the chest disclosed some foci interpreted as metastases. Ultrasound examination of the abdomen, liver, and spleen and results of bone scan were normal. Neurologic, ophthalmologic, and gynecologic examinations also showed no abnormalities. Mammography revealed a mass in the left breast, and the biopsy specimen confirmed the diagnosis of adenocarcinoma. Because of the high estrogen receptor concentration of the tumor, hormonal therapy was started with a daily dose
Volume 19 Number 2, Part 2 Auf,ust 1988
Subacute cutaneous L E and breast cancer
407
Fig. 1. Plaques arranged in rings and arcs on the chest.
Fig. 2. Annular lesions on the back similar to those on the chest.
of 20 mg tamoxifen. After 6 months of this therapy, complete clearing of the skin lesions was observed, the patient's general condition improved, and a partial regression of the tumor and of the metastases was noted. A few months later the patient gained weight and experienced drowsiness, constipation, and hair loss. The diagnosis of primary hypothyroidism was confirmed by thyroxin (0.9 I~g/dl) tests and high levels of thyroid-stimulating hormone. Although thyroid microsomal antibodies with a titer of 1:2500 were present, there were no thyroid globulin antibodies. The patient was treated with eltroxine, which improved her condition.
tosis occurs before tumor development. However, in practice it is often difficult to ascertain which disease comes first, and therefore this criterion is not always helpful. 2. Both the dermatosis and the tumor should follow a parallel course. This means that if the tumor is removed, the dermatosis clears, conversely, if the tumor recurs, the dermatosis relapses. The parallelism is not difficult to prove when the tumor is removed surgically, but with chemotherapy or hormonal therapy the medication may have nonspecific effects that could suppress the dermatosis without any relation to the tumor. Therefore this criterion is not altogether helpful either. The concept of a paraneoplastic syndrome becomes important only if the skin manifestations help in the recognition of an underlying malignancy. Whether subacute cutaneous lupus erythematosus meets McLean's two criteria is difficult to ascertain. To the best of our knowledge, in 1986 Kuhn and Kaufmann 6 described the only case of this disease associated with malignancy. Their 68-year-old patient suffered from subacute cutaneous lupus erythematosus concomitant with gastric carcinoma. Successful surgery of the tumor resulted in healing of the skin lesions. Our patient, who had subacute cutaneous lupus erythematosus and breast carcinoma, was unaware of her malignant disease and had consulted us only after her dermatosis developed. At this point she already had lung metastases. The hypothyroidism that de-
DISCUSSION It is not uncommon that skin manifestations are the first signs of various types of malignancies, and they often appear before clinical or laboratory findings are available. 2 For many years the concurrence of autoimmune disease, such as systemic lupus erythematosus, with malignancy has been recognized with increased frequency) '4 The reason for this association is obscure, and the question remains whether it constitutes a paraneoplastic syndrome. McLean 5 presents a review of Curth's criteria for the relationship between dermatosis and a malignant internal disease. He narrowed the definition of paraneoplastic syndrome to two essential criteria: 1. The dermatosis must appear after the development of the malignant tumor and cannot be considered a paraneoplastic syndrome if the derma-
Journal of the American Academy of Dermatology
408 S c h e w a c h - M i l l e t et al.
veloped could be interpreted as an additional manifestation of her immunodeficiency. When there is an association between autoimmune and neoplastic disease, the autoimmune disease can precede, coexist, or follow the diagnosis of malignancy. Several explanations have been given for these sequences. 7's'9 When the tumor comes first, the autoimmune phenomenon may be caused by the host's attempt at recognition and suppression of microfoci of tumor. When the autoimmune disease precedes the malignancy, the deficient immune surveillance may be responsible for the development of the tumor. A third possibility is that the autoimmune phenomenon and malignancy are two independent diseases to which the patient is predisposed by the same immunosuppressive factors. In our case, although the first clinical manifestation was the slcin eruption, it was obvious that the patient's breast cancer had been present for some time because she already had pulmonary metastases. The dermatosis disappeared 6 months after therapy was begun, at which time regression of the tumor mass and metastases was noted. This progression would satisfy McLean's second criterion for paraneoplastic disease if it were certain that the hormonal treatment had no direct effect on the dermatosis and that the improvement of the
skin was a consequence of the tumor regression only. We hope that our interesting case will help alert the clinician to the possibility that subacute cutaneous lupus erythematosus can be associated with malignant disease. REFERENCES 1. Sontheimer RD, Gillian IJR. Subacute cutaneous lupus erythematous: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 1979;115:1409-15. 2. Skolnick M, Mainman ER. Erythema gyratum repens with metastatic adenocarcinoma. Arch Dermatol 1975; I i 1:227-9. 3. Chuong JJH, Livstone EM, Barwick KW. Systemic lupus erythematosus and gastric carcinoma: a report of two cases and a critical review of the literature. Am J Gastroenterol 1982;77:611-3. 4. Blanc D, Kienzler JL. Lupus erythematosus gyratus repens: report of a case associated with a lung carcinoma. Clin Exp Dermatol 1982;7:129-34. 5. McLean DJ. Cutaneous paraplastic syndromes. Arch Dcrmatol 1986; ! 22:765-7. 6. Kuhn A, Kaufmann I. Subacute cutaneous lupus erythematosus as a paraneoplastic syndrome. Z Hautkr 1986; 61:581-3. 7. Efremidis A, Eiser AR, Grishman E, Rosenberg V. Hodgkin's lymphoma in an adolescent with systemic lupus erythematosus. Cancer 1984;53:142-6. 8. Milligan DW, Chang JG. Systemic lupus erythematosus and lymphoma. Acta Haematol 1980;64:109-10. 9. Agudelo C, Schumacher HR, Glick JH, Molena J. NonHodgkin's lymphoma in systemic lupus erythematosus. Rheumatology 1984;8:69-78.