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Pseudo-mycosis fungoides in a patient taking clonazepam andfluoxetine
304
Brief communications
male and 14, female. Of the remaining 18 noninfected offspring,, nine were male and nine were female. Males and females were also equally represented within statistical limits in infected and noninfected parents. Five uninfected offspring of infected parents who married uninfected palmers did not have infected children. The pedigrees show a familial pattem and one that was compatible with autosomal dominant inheritance because every child in the pedigrees with DSO had at least one parent who also had DSO. There was only one skipped generation without DSO in any of the pedigrees (1 of 22 marriages). Seventeen persons who were married to an
Journal of the American Academy of Dermatology February 1996
infected partner for 18 to 60 years never had an infection. These pedigrees show that T. rubrum infection may be familial, typically presenting as DSO with a concomitant infection of the soles. REFERENCES 1. English MD. Trichophyton mbrum infection in families. Br Med J 1957;1:744-6. 2. Many H, Derbes VJ, Friedman L. Trichophyton rubmm: exposure and infection within household groups. Arch Dermatol 1960;82:6-9. 3. Zais N. Onychomycosis. Arch Dermatol 1972;105:263-74.
Pseudo-mycosis fungoides in a patient taking clonazepam and fluoxetine Kenneth B. Gordon, MD, a Joan Guitart, MD, a Timothy Kuzel, MD, d Dominique Salard, MD, b Ouahid Bakouche, MD, b Peter Domer, MI), c Henry Roenigk, MD, a and Steven Rosen, M D d
Chicago, Illinois
A cutaneous hypersensitivity syndrome resembling mycosis fungoides has been described as a reaction to drugs, particularly to phenytoin and carbamazapine. This syndrome has been called pseudomycosis fungoides. W e describe a cutaneous reaction simulating mycosis fungoides in a patient taking fluoxefine and clonazepam. CASE REPORT A 45-year-old man had a rapidly progressing pmritic dermatitis of 2 months' duration that began on his left shoulder and spread to his trunk and extremities. He had begun therapy with fluoxetine for depression 10 months before the onset of skin lesions and clonazepam for restless leg syndrome 3 months before presentation. He was taking no other medications. From the Departments of Dermatology? Medicine,Molecular Pharmacology and Biologic Chemistry,b Phorson-GoodallLaboratory, Department of Pathology,r and Robert Lurie Cancer Center,d Northwestern UniversityMedical School. Reprint requests: Joan Guitart, MD, Department of Dermatology, Northwestern University Medical School, 330 E. Chicago Ave., Tarry 4th Floor, Chicago, IL 60611. J AM ACADDm~IATOL1996;34:304-6. C6pyright 9 1996 by the AmericanAcademy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/54/67783
Examination revealed numerous, irregular, erythematous, scaly patches and plaques on his back, abdomen, and extremities (Fig. 1). No lymphadenopathy or hepatosplenomegaly was present. A skin biopsy specimen showed hyperkeratosis, spongiosis, focal Pautrier's microabscesses, and a moderately dense infiltrate of lymphocytes with hyperconvoluted nuclei in the papillary dennis, consistent with cutaneous T-cell lymphoma (Fig. 2). Resuits or findings of complete blood cell count, serum chemistries, S~zary cell count, chest radiography, and computed tomographic scanning of his chest and abdomen were within normal limits. Southern blot analysis of the B-chain T-cell receptor gene of the patient's cutaneous infiltrate showed a novel rearranged band that suggested a clonal T-cell proliferation. The diagnosis of mycosis fungoides was made and the patient was told to discontinue all medications in anticipation of treatment. Four weeks later the cutaneous lesions had completely cleared. A skin biopsy specimen taken from a previously affected area showed only mild chronic perivascular dermatitis with no cellular atypia or epidermotropism. A lymphocyte stimulation assay I showed a proliferation of the patient's lymphocytes in response to clonazepam but not to control substances or fluoxetine. As of this writing, the patient had had no clinical recurrence of his cutaneous disease for 14 months.
Journal of the AmericanAcademyof Dermatology Volume 34, Number2, Part 1
Brief communications
305
Fig. 1. Well-demarcated scaly erythematous plaques on anterior aspect of the right arm.
Fig. 2. Photomicrograph shows spongiosis, moderately dense lymphocytic infiltrate, and Pautrier's microabscess formation. (Hematoxylin-eosin stain; original magnification xl00.)
DISCUSSION
Adverse reactions to medications simulating various forms of malignant lymphoma have been described. The pseudolymphoma syndrome with fever, erythroderma, lymphadenopathy, and eosinophilia is a hypersensitivity response to phenytoin and carbamazapine.2 A rarer response resembling mycosis fungoides has also been reported with these drugs. 2-4 Recently, other drugs, such as angiotensinconverting enzyme inhibitors, have been implicated in similar reactions.5,6 The mechanism for the development of pseudolymphoma is thought to be antigenic stimulation of lymphocytes and an associated decrease in suppressor T-cell activity.7,8
Our patient demonstrated many of the characteristic clinical and histologic features of mycosis fungoides. Our finding of a clonal population of T lymphocytes is unusual for pseudolymphoma but is consistent with a clone emerging from antigen stimulation without normal suppressor T cell function. This finding and the lymphocyte proliferation when challenged with clonazepam suggest that the mechanism for the eruption in this patient is through T-cell-mediated hypersensitivity to the offending drug. Margo et al.9 described a patient taking clonazepam with an eruption suggestive of mycosis fungoides. Failure to identify pseudo-mycosis fungoides has
306
Brief communications
resulted in unnecessary systemic chemotherapy with significant morbidity. 2'I~ W e r e c o m m e n d withdrawal o f all noncritical medications to identify any possible adverse cutaneous reactions that might be simulating mycosis fungoides. REFERENCES 1. Mosmann T. Rapid colorimeWicassay for cellular growth and survival: application to proliferation and cytotoxic assay. J Immunol Methods 1983;65:55-63. 2. Schreiber MM, McGregor JC. Pseudolymphoma syndrome: a sensitivity to anticonvulsant drugs. Arch Dermatol 1968;97:297-300. 3. Welykyj S, Gradini R, Nakao J, et al. Carbamazapine-induced eruption histologically mimicking mycosis fungoides. J Cutan Pathol 1990;17:I 11-6. 4. Rijlaarsdam U, Scheffer E, Meijer CJEM, et al. Mycosis funogides-like lesions associated with phenytoin and carbamazepine therapy. J AM ACADDm~aATOL1991;24:21620.
Journal of the American Academy of Dermatology February 1996
5. Kardaun SH, Scheffer E, Vermeer BJ. Drag-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118:845-52. 6. Fumess PN, Goodfield MJ, MacLennan KA, et al. Severe cutaneous reactions to captopril and enalapril: histologic study and comparison with early mycosis fungoides. J Clin Pathol 1986;39:902-7. 7. Charlesworth EN. Phenytoin-induced pseudolymphoma syndrome: an immunologic study. Arch Derrnatol 1977;113:447-80. 8. Rosenthal CA, Noguera CA, Coppola A, et al. Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin and lymphocyte dysregulation. Cancer 1982;49:2305-14. 9. Margo C, Cmwson N, Hatta T, et al. A 47-year-old woman with several large chronic scaling plaques. Fitzpatrick's J Clin Dermatol 1993;1:24-8. 10. Rosenfeld S, Swiller AI, Shenoy YM, et al. Syndrome simulating lymphosarcoma induced by diphenylhydantoin sodium. JAMA 1961;176:491-3.
Intracranial malignant meningioma mimicking frontalis-associated lipoma of the forehead Maxwell A. Fung, MD, R o y C. Grekin, MD, and Richard B. Odom, M D
San Francisco, California Malignant meningioma is an u n c o m m o n neoplasm o f the central nervous system that rarely presents as an extracranial soft tissue mass. These malignancies m a y or may not be associated with intracranial lesions. In primary extracranial malignant meningioma, the tumor m a y arise t~om ectopic nests o f arachnoid cells that follow cranial nerve pathways without involvement o f b o n y structures. 1 In the case o f intracranial malignant meningioma, the subcutaneous soft tissue mass extends directly f r o m an underlying osteolytic skull lesion and intracranial tumor. 2 Subfascial, or ffontalis-associated, lipomas o f the
From the Departmentof Dermatology,Universityof California,San Francisco. Reprintrequests:MaxwellA. Fung,MD, DepartmentofDermatology, University of Calffomia, San Francisco,400 Parnassus Ave., 3rd Floor, San Francisco,CA 94143. J AMACADDmuvtnTOL1996;34:306-7. Copyright 9 1996 by the AmericanAcademyof Dermatology,Inc. 0190-9622/96 $5.00+ 0 16/54/67558
forehead were first described in Europe 3 and more recently in the American dermatologic literature. 4 T h e differential diagnosis includes epidermoid cyst, pilar cyst, and, occasionally, dermoid cyst. W e observed an intracranial malignant meningio m a that bore a striking resemblance to a subfascial lipoma. CASE REPORT A 33-year-old man had a 3-month history of a progressively enlarging painless nodule on the forehead. He reported mild dizziness, nausea, and a headache that was relieved by acetaminophen. Examination revealed a rubbery, flesh-colored, dome-shaped, nontender subcutaneous nodule 4 cm in diameter whose coveting skin was slightly moveable. A hard rim was under the skin encircling the base of the lesion. No central pore was present. A diagnosis of subfrontalis lipoma was considered. During the next several days, however, the patient's headache worsened. Examination revealed bilateral papilledema but no focal neurologic deficits. A computed tomographic scan of the head showed a large intracranial
Brief communications
male and 14, female. Of the remaining 18 noninfected offspring,, nine were male and nine were female. Males and females were also equally represented within statistical limits in infected and noninfected parents. Five uninfected offspring of infected parents who married uninfected palmers did not have infected children. The pedigrees show a familial pattem and one that was compatible with autosomal dominant inheritance because every child in the pedigrees with DSO had at least one parent who also had DSO. There was only one skipped generation without DSO in any of the pedigrees (1 of 22 marriages). Seventeen persons who were married to an
Journal of the American Academy of Dermatology February 1996
infected partner for 18 to 60 years never had an infection. These pedigrees show that T. rubrum infection may be familial, typically presenting as DSO with a concomitant infection of the soles. REFERENCES 1. English MD. Trichophyton mbrum infection in families. Br Med J 1957;1:744-6. 2. Many H, Derbes VJ, Friedman L. Trichophyton rubmm: exposure and infection within household groups. Arch Dermatol 1960;82:6-9. 3. Zais N. Onychomycosis. Arch Dermatol 1972;105:263-74.
Pseudo-mycosis fungoides in a patient taking clonazepam and fluoxetine Kenneth B. Gordon, MD, a Joan Guitart, MD, a Timothy Kuzel, MD, d Dominique Salard, MD, b Ouahid Bakouche, MD, b Peter Domer, MI), c Henry Roenigk, MD, a and Steven Rosen, M D d
Chicago, Illinois
A cutaneous hypersensitivity syndrome resembling mycosis fungoides has been described as a reaction to drugs, particularly to phenytoin and carbamazapine. This syndrome has been called pseudomycosis fungoides. W e describe a cutaneous reaction simulating mycosis fungoides in a patient taking fluoxefine and clonazepam. CASE REPORT A 45-year-old man had a rapidly progressing pmritic dermatitis of 2 months' duration that began on his left shoulder and spread to his trunk and extremities. He had begun therapy with fluoxetine for depression 10 months before the onset of skin lesions and clonazepam for restless leg syndrome 3 months before presentation. He was taking no other medications. From the Departments of Dermatology? Medicine,Molecular Pharmacology and Biologic Chemistry,b Phorson-GoodallLaboratory, Department of Pathology,r and Robert Lurie Cancer Center,d Northwestern UniversityMedical School. Reprint requests: Joan Guitart, MD, Department of Dermatology, Northwestern University Medical School, 330 E. Chicago Ave., Tarry 4th Floor, Chicago, IL 60611. J AM ACADDm~IATOL1996;34:304-6. C6pyright 9 1996 by the AmericanAcademy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/54/67783
Examination revealed numerous, irregular, erythematous, scaly patches and plaques on his back, abdomen, and extremities (Fig. 1). No lymphadenopathy or hepatosplenomegaly was present. A skin biopsy specimen showed hyperkeratosis, spongiosis, focal Pautrier's microabscesses, and a moderately dense infiltrate of lymphocytes with hyperconvoluted nuclei in the papillary dennis, consistent with cutaneous T-cell lymphoma (Fig. 2). Resuits or findings of complete blood cell count, serum chemistries, S~zary cell count, chest radiography, and computed tomographic scanning of his chest and abdomen were within normal limits. Southern blot analysis of the B-chain T-cell receptor gene of the patient's cutaneous infiltrate showed a novel rearranged band that suggested a clonal T-cell proliferation. The diagnosis of mycosis fungoides was made and the patient was told to discontinue all medications in anticipation of treatment. Four weeks later the cutaneous lesions had completely cleared. A skin biopsy specimen taken from a previously affected area showed only mild chronic perivascular dermatitis with no cellular atypia or epidermotropism. A lymphocyte stimulation assay I showed a proliferation of the patient's lymphocytes in response to clonazepam but not to control substances or fluoxetine. As of this writing, the patient had had no clinical recurrence of his cutaneous disease for 14 months.
Journal of the AmericanAcademyof Dermatology Volume 34, Number2, Part 1
Brief communications
305
Fig. 1. Well-demarcated scaly erythematous plaques on anterior aspect of the right arm.
Fig. 2. Photomicrograph shows spongiosis, moderately dense lymphocytic infiltrate, and Pautrier's microabscess formation. (Hematoxylin-eosin stain; original magnification xl00.)
DISCUSSION
Adverse reactions to medications simulating various forms of malignant lymphoma have been described. The pseudolymphoma syndrome with fever, erythroderma, lymphadenopathy, and eosinophilia is a hypersensitivity response to phenytoin and carbamazapine.2 A rarer response resembling mycosis fungoides has also been reported with these drugs. 2-4 Recently, other drugs, such as angiotensinconverting enzyme inhibitors, have been implicated in similar reactions.5,6 The mechanism for the development of pseudolymphoma is thought to be antigenic stimulation of lymphocytes and an associated decrease in suppressor T-cell activity.7,8
Our patient demonstrated many of the characteristic clinical and histologic features of mycosis fungoides. Our finding of a clonal population of T lymphocytes is unusual for pseudolymphoma but is consistent with a clone emerging from antigen stimulation without normal suppressor T cell function. This finding and the lymphocyte proliferation when challenged with clonazepam suggest that the mechanism for the eruption in this patient is through T-cell-mediated hypersensitivity to the offending drug. Margo et al.9 described a patient taking clonazepam with an eruption suggestive of mycosis fungoides. Failure to identify pseudo-mycosis fungoides has
306
Brief communications
resulted in unnecessary systemic chemotherapy with significant morbidity. 2'I~ W e r e c o m m e n d withdrawal o f all noncritical medications to identify any possible adverse cutaneous reactions that might be simulating mycosis fungoides. REFERENCES 1. Mosmann T. Rapid colorimeWicassay for cellular growth and survival: application to proliferation and cytotoxic assay. J Immunol Methods 1983;65:55-63. 2. Schreiber MM, McGregor JC. Pseudolymphoma syndrome: a sensitivity to anticonvulsant drugs. Arch Dermatol 1968;97:297-300. 3. Welykyj S, Gradini R, Nakao J, et al. Carbamazapine-induced eruption histologically mimicking mycosis fungoides. J Cutan Pathol 1990;17:I 11-6. 4. Rijlaarsdam U, Scheffer E, Meijer CJEM, et al. Mycosis funogides-like lesions associated with phenytoin and carbamazepine therapy. J AM ACADDm~aATOL1991;24:21620.
Journal of the American Academy of Dermatology February 1996
5. Kardaun SH, Scheffer E, Vermeer BJ. Drag-induced pseudolymphomatous skin reactions. Br J Dermatol 1988;118:845-52. 6. Fumess PN, Goodfield MJ, MacLennan KA, et al. Severe cutaneous reactions to captopril and enalapril: histologic study and comparison with early mycosis fungoides. J Clin Pathol 1986;39:902-7. 7. Charlesworth EN. Phenytoin-induced pseudolymphoma syndrome: an immunologic study. Arch Derrnatol 1977;113:447-80. 8. Rosenthal CA, Noguera CA, Coppola A, et al. Pseudolymphoma with mycosis fungoides manifestations, hyperresponsiveness to diphenylhydantoin and lymphocyte dysregulation. Cancer 1982;49:2305-14. 9. Margo C, Cmwson N, Hatta T, et al. A 47-year-old woman with several large chronic scaling plaques. Fitzpatrick's J Clin Dermatol 1993;1:24-8. 10. Rosenfeld S, Swiller AI, Shenoy YM, et al. Syndrome simulating lymphosarcoma induced by diphenylhydantoin sodium. JAMA 1961;176:491-3.
Intracranial malignant meningioma mimicking frontalis-associated lipoma of the forehead Maxwell A. Fung, MD, R o y C. Grekin, MD, and Richard B. Odom, M D
San Francisco, California Malignant meningioma is an u n c o m m o n neoplasm o f the central nervous system that rarely presents as an extracranial soft tissue mass. These malignancies m a y or may not be associated with intracranial lesions. In primary extracranial malignant meningioma, the tumor m a y arise t~om ectopic nests o f arachnoid cells that follow cranial nerve pathways without involvement o f b o n y structures. 1 In the case o f intracranial malignant meningioma, the subcutaneous soft tissue mass extends directly f r o m an underlying osteolytic skull lesion and intracranial tumor. 2 Subfascial, or ffontalis-associated, lipomas o f the
From the Departmentof Dermatology,Universityof California,San Francisco. Reprintrequests:MaxwellA. Fung,MD, DepartmentofDermatology, University of Calffomia, San Francisco,400 Parnassus Ave., 3rd Floor, San Francisco,CA 94143. J AMACADDmuvtnTOL1996;34:306-7. Copyright 9 1996 by the AmericanAcademyof Dermatology,Inc. 0190-9622/96 $5.00+ 0 16/54/67558
forehead were first described in Europe 3 and more recently in the American dermatologic literature. 4 T h e differential diagnosis includes epidermoid cyst, pilar cyst, and, occasionally, dermoid cyst. W e observed an intracranial malignant meningio m a that bore a striking resemblance to a subfascial lipoma. CASE REPORT A 33-year-old man had a 3-month history of a progressively enlarging painless nodule on the forehead. He reported mild dizziness, nausea, and a headache that was relieved by acetaminophen. Examination revealed a rubbery, flesh-colored, dome-shaped, nontender subcutaneous nodule 4 cm in diameter whose coveting skin was slightly moveable. A hard rim was under the skin encircling the base of the lesion. No central pore was present. A diagnosis of subfrontalis lipoma was considered. During the next several days, however, the patient's headache worsened. Examination revealed bilateral papilledema but no focal neurologic deficits. A computed tomographic scan of the head showed a large intracranial