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Psoriasiform mycosis fungoides with fatal outcome after treatment with cyclosporine
LETTERS
Psoriasiform mycosis fungoides with fatal outcome after treatment with cyclosporine To the Editor: We report the course of a 52-year-old woman who was considered to have severe psoriasis and was treated with cyclosporine, which was followed by rapid development of an aggressive cutaneous T-cell lymphoma and fatal outcome. Retrospective studies revealed that she had mycosis fungoides (MF), which clinically and microscopically simulated psoriasis from the onset. A 52-year-old woman was seen on November 4, 1998, at the University of California San Francisco (UCSF) Psoriasis and Skin Treatment Center; she had an 8-year history of a generalized pruritic eruption. A biopsy specimen from the leg obtained on September
Fig 1. Lesions on thigh 2 days after patient had taken cyclosporine for 21 days.
Fig 2. Biopsy specimen from lesion shown in Fig 1. There is a bandlike infiltrate in the superficial dermis and a patchy infiltrate in the mid and deep dermis (A). Most cells in the papillary dermis are blasts (B).
22, 1992, was originally interpreted at UCSF as subacute to chronic spongiotic dermatitis, but the interpretation was subsequently revised, after review of a subsequent biopsy specimen and more complete history, on September 17, 1997, to evolving psoriasis. A biopsy specimen from the torso obtained on January 9, 1997, was identified elsewhere as spongiotic dermatitis. A J AM ACAD DERMATOL
biopsy specimen from the left scapular area obtained on September 4, 1997, was interpreted at UCSF as psoriasiform dermatitis, with features favoring psoriasis. Examination revealed widespread psoriasiform plaques, some of which were indurated, involving 30% to 40% of the skin. Medical history was remarkable for osteoporosis, sciatica, constipation, and inJULY 2002
155
156 Letters
somnia. Previous therapies included ultraviolet B light, 6-thioguanine, topical calcipotriol and corticosteroids, ketoconazole, and tazarotene. Current medications included methotrexate (12.5 mg every 2 weeks), hydroxyzine, naproxen, medroxyprogesterone, lorazepam, and topical calcipotriol. From November 16, 1998 to December 18, 1998, she received combination UVB and 2% or 5% crude coal tar ointment and the same dose of methotrexate and experienced moderate improvement. Results of complete blood cell count and blood chemistries were normal. On February 1, 1999, she presented with palmar and plantar desquamation and widespread erythematous patches and plaques. On February 2, 1999, administration of cyclosporine was started at a dose of 4.2 mg/kg per day. Blood pressure was 134/90 mm Hg. On day 21 of cyclosporine therapy, 3 “nodules” were noted on the anterior thighs (Fig 1). cyclosporine was stopped. Punch biopsy specimens from all 3 lesions were identified as late plaque stage MF because they showed dense dermal infiltrates of large lymphocytes with features of “blasts” and marked infiltration of the epidermis with only scant spongiosis (Fig 2). The patient was then referred to the UCSF Cutaneous Lymphoma Clinic. The earlier 1997 biopsy specimen from the torso was reviewed. This showed a moderately dense lymphocytic infiltrate along the epidermal-dermal junction in association with marked spongiosis and crusting. In retrospect, we believe that this biopsy specimen represented an early stage of MF that was not recognizable, because the lymphoid infiltrate was disguised by secondary inflammatory changes, although it is also possible that the patient had both psoriasis and MF. Subsequent studies, in which the polymerase chain reaction was used for detection of T-cell receptor gene rearrangement, revealed a clonal population in the 1992 specimen from the leg. Genotypic analysis of the 1997 biopsy specimens could not be done because of technical difficulties. Four weeks after cyclosporine therapy was stopped, biopsy specimens were taken from enlarged lymph nodes in the groin and axilla. These specimens were interpreted at Stanford University as diffuse large cell lymphoma consistent with progression of MF. More recently, genotypic analysis with the polymerase chain reaction technique revealed that both the 1992 biopsy specimen from the leg and the 1999 biopsy specimen from one of the thigh plaques yielded clonal TCR-␥ gene rearrangements that were identical on sequence analysis. The patient did not respond to treatment with in-
J AM ACAD DERMATOL JULY 2002
terferon alfa, combination cyclophosphamide, Adriamycin, vincristine, and prednisone, and total skin electron beam therapy and died of large cell lymphoma almost 1 year after cyclosporine therapy was started. Cooper et al1 reported the only prospective study of treatment of cutaneous T-cell lymphoma with cyclosporine. Only 2 of 11 patients had responses and these were temporary. A literature review revealed 5 reports involving 8 patients with cutaneous T-cell lymphoma in whom progressive disease developed within 4 months after administration of cyclosporine was started.2-6 These included 4 probable treatment-related deaths.2-5 We believe this case report is important for at least 2 reasons: (1) it illustrates the difficulty in distinguishing some cases of MF from psoriasis, both clinically and pathologically; and (2) it is another example of conversion of MF to a highly aggressive lymphoma with fatal outcome after treatment with cyclosporine. Physicians should be particularly cautious in treating atypical psoriasiform dermatoses with cyclosporine. Herschel S. Zackheim, MDa John Koo, MDa Philip E. LeBoit, MDa,b Timothy H. McCalmont, MDa,b Paul H. Bowman, MDa Mohammed Kashani-Sabet, MDa Carol Jones, BAc James Zehnder, MDc Department of Dermatologya Department of Pathologyb University of California, San Francisco Department of Pathologyc Stanford University School of Medicine Correspondence to: Herschel S. Zackheim, MD 2327 Branner Dr Menlo Park, CA 94025 E-mail: [email protected] REFERENCES 1. Cooper DL, Braverman IM, Sarris H, Durivage HJ, Saidman BH, Davis CA, et al. Cyclosporine treatment of refractory T-cell lymphomas. Cancer 1993;71:2335-41. 2. Moreland AA, Robertson DB, Heffner LT. Treatment of cutaneous T-cell lymphoma with cyclosporin A. J Am Acad Dermatol 1985; 12:886-7. 3. Thomsen K, Wantzin GL. Extracutaneous spreading with fatal outcome of mycosis fungoides in a patient treated with ciclosporin A: a word of caution. Dermatologica 1987;174:236-8. 4. Jensen JR, Thestrup-Pedersen K, Zachariae H, Sogaard H. Cyclosporin A therapy for mycosis fungoides. Arch Dermatol 1987;123: 160-3.
Letters 157
J AM ACAD DERMATOL VOLUME 47, NUMBER 1
5. Kreis W, Budman DR, Shapiro PE. Cyclosporin A (cyclosporine) in the treatment of cutaneous T-cell lymphoma (mycosis fungoides). J Am Acad Dermatol 1988;18:1138-40. 6. Street ML, Muller SA, Pittlekow MR. Cyclosporine in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol 1990;23:1084-9. 16/8/120571 doi:10.1067/mjd.2002.120571
Psoriasiform mycosis fungoides with fatal outcome after treatment with cyclosporine To the Editor: We report the course of a 52-year-old woman who was considered to have severe psoriasis and was treated with cyclosporine, which was followed by rapid development of an aggressive cutaneous T-cell lymphoma and fatal outcome. Retrospective studies revealed that she had mycosis fungoides (MF), which clinically and microscopically simulated psoriasis from the onset. A 52-year-old woman was seen on November 4, 1998, at the University of California San Francisco (UCSF) Psoriasis and Skin Treatment Center; she had an 8-year history of a generalized pruritic eruption. A biopsy specimen from the leg obtained on September
Fig 1. Lesions on thigh 2 days after patient had taken cyclosporine for 21 days.
Fig 2. Biopsy specimen from lesion shown in Fig 1. There is a bandlike infiltrate in the superficial dermis and a patchy infiltrate in the mid and deep dermis (A). Most cells in the papillary dermis are blasts (B).
22, 1992, was originally interpreted at UCSF as subacute to chronic spongiotic dermatitis, but the interpretation was subsequently revised, after review of a subsequent biopsy specimen and more complete history, on September 17, 1997, to evolving psoriasis. A biopsy specimen from the torso obtained on January 9, 1997, was identified elsewhere as spongiotic dermatitis. A J AM ACAD DERMATOL
biopsy specimen from the left scapular area obtained on September 4, 1997, was interpreted at UCSF as psoriasiform dermatitis, with features favoring psoriasis. Examination revealed widespread psoriasiform plaques, some of which were indurated, involving 30% to 40% of the skin. Medical history was remarkable for osteoporosis, sciatica, constipation, and inJULY 2002
155
156 Letters
somnia. Previous therapies included ultraviolet B light, 6-thioguanine, topical calcipotriol and corticosteroids, ketoconazole, and tazarotene. Current medications included methotrexate (12.5 mg every 2 weeks), hydroxyzine, naproxen, medroxyprogesterone, lorazepam, and topical calcipotriol. From November 16, 1998 to December 18, 1998, she received combination UVB and 2% or 5% crude coal tar ointment and the same dose of methotrexate and experienced moderate improvement. Results of complete blood cell count and blood chemistries were normal. On February 1, 1999, she presented with palmar and plantar desquamation and widespread erythematous patches and plaques. On February 2, 1999, administration of cyclosporine was started at a dose of 4.2 mg/kg per day. Blood pressure was 134/90 mm Hg. On day 21 of cyclosporine therapy, 3 “nodules” were noted on the anterior thighs (Fig 1). cyclosporine was stopped. Punch biopsy specimens from all 3 lesions were identified as late plaque stage MF because they showed dense dermal infiltrates of large lymphocytes with features of “blasts” and marked infiltration of the epidermis with only scant spongiosis (Fig 2). The patient was then referred to the UCSF Cutaneous Lymphoma Clinic. The earlier 1997 biopsy specimen from the torso was reviewed. This showed a moderately dense lymphocytic infiltrate along the epidermal-dermal junction in association with marked spongiosis and crusting. In retrospect, we believe that this biopsy specimen represented an early stage of MF that was not recognizable, because the lymphoid infiltrate was disguised by secondary inflammatory changes, although it is also possible that the patient had both psoriasis and MF. Subsequent studies, in which the polymerase chain reaction was used for detection of T-cell receptor gene rearrangement, revealed a clonal population in the 1992 specimen from the leg. Genotypic analysis of the 1997 biopsy specimens could not be done because of technical difficulties. Four weeks after cyclosporine therapy was stopped, biopsy specimens were taken from enlarged lymph nodes in the groin and axilla. These specimens were interpreted at Stanford University as diffuse large cell lymphoma consistent with progression of MF. More recently, genotypic analysis with the polymerase chain reaction technique revealed that both the 1992 biopsy specimen from the leg and the 1999 biopsy specimen from one of the thigh plaques yielded clonal TCR-␥ gene rearrangements that were identical on sequence analysis. The patient did not respond to treatment with in-
J AM ACAD DERMATOL JULY 2002
terferon alfa, combination cyclophosphamide, Adriamycin, vincristine, and prednisone, and total skin electron beam therapy and died of large cell lymphoma almost 1 year after cyclosporine therapy was started. Cooper et al1 reported the only prospective study of treatment of cutaneous T-cell lymphoma with cyclosporine. Only 2 of 11 patients had responses and these were temporary. A literature review revealed 5 reports involving 8 patients with cutaneous T-cell lymphoma in whom progressive disease developed within 4 months after administration of cyclosporine was started.2-6 These included 4 probable treatment-related deaths.2-5 We believe this case report is important for at least 2 reasons: (1) it illustrates the difficulty in distinguishing some cases of MF from psoriasis, both clinically and pathologically; and (2) it is another example of conversion of MF to a highly aggressive lymphoma with fatal outcome after treatment with cyclosporine. Physicians should be particularly cautious in treating atypical psoriasiform dermatoses with cyclosporine. Herschel S. Zackheim, MDa John Koo, MDa Philip E. LeBoit, MDa,b Timothy H. McCalmont, MDa,b Paul H. Bowman, MDa Mohammed Kashani-Sabet, MDa Carol Jones, BAc James Zehnder, MDc Department of Dermatologya Department of Pathologyb University of California, San Francisco Department of Pathologyc Stanford University School of Medicine Correspondence to: Herschel S. Zackheim, MD 2327 Branner Dr Menlo Park, CA 94025 E-mail: [email protected] REFERENCES 1. Cooper DL, Braverman IM, Sarris H, Durivage HJ, Saidman BH, Davis CA, et al. Cyclosporine treatment of refractory T-cell lymphomas. Cancer 1993;71:2335-41. 2. Moreland AA, Robertson DB, Heffner LT. Treatment of cutaneous T-cell lymphoma with cyclosporin A. J Am Acad Dermatol 1985; 12:886-7. 3. Thomsen K, Wantzin GL. Extracutaneous spreading with fatal outcome of mycosis fungoides in a patient treated with ciclosporin A: a word of caution. Dermatologica 1987;174:236-8. 4. Jensen JR, Thestrup-Pedersen K, Zachariae H, Sogaard H. Cyclosporin A therapy for mycosis fungoides. Arch Dermatol 1987;123: 160-3.
Letters 157
J AM ACAD DERMATOL VOLUME 47, NUMBER 1
5. Kreis W, Budman DR, Shapiro PE. Cyclosporin A (cyclosporine) in the treatment of cutaneous T-cell lymphoma (mycosis fungoides). J Am Acad Dermatol 1988;18:1138-40. 6. Street ML, Muller SA, Pittlekow MR. Cyclosporine in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol 1990;23:1084-9. 16/8/120571 doi:10.1067/mjd.2002.120571