Case Report Dermatology 1992; 185:314-315
P. Paquet J. Arrese Estrada G.E. Pierard
Oral Cyclosporin and Alopecia areata
Departments of Dermatology and Dcrmatopathology, University of Liege. Belgium
Key Words Cyclosporin Alopecia areata Immunohistochcmistry Lymphocyte
Abstract A 30-year-old woman with severe alopecia areata of the scalp was treated with oral cyclosporin for 3 months. Clinical, histological and immunohistochemical assessments failed to reveal any improvement.
Introduction Many modalities have been used in the treatment of alo pecia areata, among them corticosteroids, ultraviolet light, contact sensitizers and irritants, and minoxidil. The efficacy of topical cyclosporin was rarely evidenced in such an indi cation [1-4], Oral cyclosporin was however considered to be more effective by clearing immune cells from the altered hair follicles [5, 6].
Skin biopsies of bald areas were taken before and after the 3month therapy. The histological features were almost identical in these samples. A dense lymphoid infiltrate abutted on the deep part of the hair follicles. Immunohistological studies using monoclonal anti bodies to activated T cells (CD45RO, UCLI11 ). helper-inducer T cells (CD4). suppressor-cytotoxic T cells (CD8). class II major histocom patibility complex (HLA-DR) and Langerhans cells (CDI) revealed a mixed population of both activated CD4 and CDS' T cells admixed with CDI and DR cells in follicular and perifollicular locations (fig. 1).
Discussion Case Report Oral cyclosporin seemed justified in treating severe alo pecia areata by its immunomodulating activity [6]. In fact, the infiltrate around the hair follicles consists predom inantly of CD4 ' T lymphocytes which could be responsible for the lesions. Cyclosporin may act specifically on these cells in reducing their activation and multiplication. Such a link between biological and therapeutic effects of cyclospo rine was recently reported in 3 out of 6 patients with severe alopecia areata [6], The clinical response was correlated with modifications in the cellular infiltrate in and around
Dr. G .E. Pierard Poparlmen! of Dermalopalliology CHU ilu Sart-Tilman B-4000 Liège (Belgium)
© 1992 Kargcr ACi. Basel 1018-8665/92/ 1X54-0314 $ 2.75/0
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A 30-ycar-old woman had had multiple large patches of alopecia areata since puberty. The lesions had been stable for the past 2 years. There was no other systemic or dermatological disease. Previous treat ments including topical minoxidil, ultraviolet light and immunother apy had previously failed. She used no medication for 4 weeks before entering the study. She was given oral cyclosporin (Sandimmun®: Sandoz. Basel. Switzerland) 3 mg/kg b.i.d. for 3 months. No biological and clinical side effects were observed. Cyclosporin concentrations in the scrum ranged from 150 to 400 ng/ml. Clinical results were very disappointing as no evident hair regrowth occurred in time.
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hair follicles. The main changes consisted of a decrease in the number of CD4' and CD8+ T cells as well as in CD1 Langerhans cells and in the expression of the HLA-DR and ICAM-1 antigens. Our findings do not concur with these observations as no beneficial clinical response and no histo logical changes were seen after a 3-month oral treatment. In our experience the inflammatory cell infiltrate pres ent in alopecia areata does not contain proliferating lym phocytes [7]. This is strikingly different from most other immune diseases such as contact dermatitis, psoriasis, lichen planus, lupus erythematosus and pseudolymphomas [8]. The apparently quiescent lymphocytes of alopecia areata could be less sensitive to cyclosporin than the prolif erative ones in other inflammatory skin diseases. Further studies on larger groups of patients are manda tory to better define a possible indication of oral cyclospo rin in severe alopecia areata. The potential long-term hazards of the drug should also be considered in such a dis ease with so easy recurrences.
Fig. 1. Dense CD45RO lymphocytic infiltrate still abutted on a hair follicle after a 3-month therapy with oral cyclosporin.
References
2
3
Thomson AW. Aldridge RD. Sewell HF: Top ical cyclosporin, in alopecia areata and nickel contact dermatitis. Lancet 1986:i:971-972. de Prost Y. Tcillac D. Paqucz F. Carrugi L. Bachelez H. Touraine R: Placebo-controlled trial of topical cyclosporin in severe alopecia areata. Lancet l986;ii:803-804. Parodi A. Rebora A: Topical cyclosporine in alopecia areata. Arch Dermatol 1987:123: 165-166.
4
5
6
Mauduit G. [.envers P. Barthélémy II. ThivoIctJ: Traitement des pelades sévères par appli cations locales dc cyclosporine A. Ann Derm Vénéréol 1987:114:507-510. Gcbhart W. Schmidt JB. Schcmpcr M. Spona J. Kopsa IL Zazgornik J: Cyclosporin-Ainduced hair growth in human renal allograft recipients and alopecia areata. Arch Dermatol Res 1986:278:238-240. Gupta AK. EllisC. Cooper K. Nickoloff B. Ho V. Chan L. Hamilton T. Tellner D. Griffiths C. Voorhccs J: Oral cyclosporine for the treat ment of alopecia areata. .1 Am Acad Dermatol 1990:22:242-250.
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8
Pidrard GE. dc la Brassinne M: Cellular activ ity in the dermis surrounding the hair bulb in alopecia areata. J Cutan Pathol 1975:2: 240-245. Pierard GE. Pierard-Franchimont C: Pattern of distribution and intensity of blastogcnesis as clues for distinguishing pseudolymphomas from lymphomas. Br J Dermatol 1983:109: 253-259.
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1
P. Paquet J. Arrese Estrada G.E. Pierard
Oral Cyclosporin and Alopecia areata
Departments of Dermatology and Dcrmatopathology, University of Liege. Belgium
Key Words Cyclosporin Alopecia areata Immunohistochcmistry Lymphocyte
Abstract A 30-year-old woman with severe alopecia areata of the scalp was treated with oral cyclosporin for 3 months. Clinical, histological and immunohistochemical assessments failed to reveal any improvement.
Introduction Many modalities have been used in the treatment of alo pecia areata, among them corticosteroids, ultraviolet light, contact sensitizers and irritants, and minoxidil. The efficacy of topical cyclosporin was rarely evidenced in such an indi cation [1-4], Oral cyclosporin was however considered to be more effective by clearing immune cells from the altered hair follicles [5, 6].
Skin biopsies of bald areas were taken before and after the 3month therapy. The histological features were almost identical in these samples. A dense lymphoid infiltrate abutted on the deep part of the hair follicles. Immunohistological studies using monoclonal anti bodies to activated T cells (CD45RO, UCLI11 ). helper-inducer T cells (CD4). suppressor-cytotoxic T cells (CD8). class II major histocom patibility complex (HLA-DR) and Langerhans cells (CDI) revealed a mixed population of both activated CD4 and CDS' T cells admixed with CDI and DR cells in follicular and perifollicular locations (fig. 1).
Discussion Case Report Oral cyclosporin seemed justified in treating severe alo pecia areata by its immunomodulating activity [6]. In fact, the infiltrate around the hair follicles consists predom inantly of CD4 ' T lymphocytes which could be responsible for the lesions. Cyclosporin may act specifically on these cells in reducing their activation and multiplication. Such a link between biological and therapeutic effects of cyclospo rine was recently reported in 3 out of 6 patients with severe alopecia areata [6], The clinical response was correlated with modifications in the cellular infiltrate in and around
Dr. G .E. Pierard Poparlmen! of Dermalopalliology CHU ilu Sart-Tilman B-4000 Liège (Belgium)
© 1992 Kargcr ACi. Basel 1018-8665/92/ 1X54-0314 $ 2.75/0
Downloaded by: Vanderbilt University Library 129.59.95.115 - 10/26/2017 4:52:49 PM
A 30-ycar-old woman had had multiple large patches of alopecia areata since puberty. The lesions had been stable for the past 2 years. There was no other systemic or dermatological disease. Previous treat ments including topical minoxidil, ultraviolet light and immunother apy had previously failed. She used no medication for 4 weeks before entering the study. She was given oral cyclosporin (Sandimmun®: Sandoz. Basel. Switzerland) 3 mg/kg b.i.d. for 3 months. No biological and clinical side effects were observed. Cyclosporin concentrations in the scrum ranged from 150 to 400 ng/ml. Clinical results were very disappointing as no evident hair regrowth occurred in time.
rj
hair follicles. The main changes consisted of a decrease in the number of CD4' and CD8+ T cells as well as in CD1 Langerhans cells and in the expression of the HLA-DR and ICAM-1 antigens. Our findings do not concur with these observations as no beneficial clinical response and no histo logical changes were seen after a 3-month oral treatment. In our experience the inflammatory cell infiltrate pres ent in alopecia areata does not contain proliferating lym phocytes [7]. This is strikingly different from most other immune diseases such as contact dermatitis, psoriasis, lichen planus, lupus erythematosus and pseudolymphomas [8]. The apparently quiescent lymphocytes of alopecia areata could be less sensitive to cyclosporin than the prolif erative ones in other inflammatory skin diseases. Further studies on larger groups of patients are manda tory to better define a possible indication of oral cyclospo rin in severe alopecia areata. The potential long-term hazards of the drug should also be considered in such a dis ease with so easy recurrences.
Fig. 1. Dense CD45RO lymphocytic infiltrate still abutted on a hair follicle after a 3-month therapy with oral cyclosporin.
References
2
3
Thomson AW. Aldridge RD. Sewell HF: Top ical cyclosporin, in alopecia areata and nickel contact dermatitis. Lancet 1986:i:971-972. de Prost Y. Tcillac D. Paqucz F. Carrugi L. Bachelez H. Touraine R: Placebo-controlled trial of topical cyclosporin in severe alopecia areata. Lancet l986;ii:803-804. Parodi A. Rebora A: Topical cyclosporine in alopecia areata. Arch Dermatol 1987:123: 165-166.
4
5
6
Mauduit G. [.envers P. Barthélémy II. ThivoIctJ: Traitement des pelades sévères par appli cations locales dc cyclosporine A. Ann Derm Vénéréol 1987:114:507-510. Gcbhart W. Schmidt JB. Schcmpcr M. Spona J. Kopsa IL Zazgornik J: Cyclosporin-Ainduced hair growth in human renal allograft recipients and alopecia areata. Arch Dermatol Res 1986:278:238-240. Gupta AK. EllisC. Cooper K. Nickoloff B. Ho V. Chan L. Hamilton T. Tellner D. Griffiths C. Voorhccs J: Oral cyclosporine for the treat ment of alopecia areata. .1 Am Acad Dermatol 1990:22:242-250.
7
8
Pidrard GE. dc la Brassinne M: Cellular activ ity in the dermis surrounding the hair bulb in alopecia areata. J Cutan Pathol 1975:2: 240-245. Pierard GE. Pierard-Franchimont C: Pattern of distribution and intensity of blastogcnesis as clues for distinguishing pseudolymphomas from lymphomas. Br J Dermatol 1983:109: 253-259.
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