Psychother Psychosom 1991;56:235-241
© 1991 S. Kargcr AG. Basel 0033-3190/91/0564-02 35S2.75/0
Application of Psychoimmunotherapy in Patients with Alopecia universalis Hideki Teshima, Hiroshi Sogawa, Koji Mizobe, Naoko Kuroki, Tetsuya Nakagawa Department of Psychosomatic Medicine. Faculty of Medicine. Kyushu University. Fukuoka. Japan
Introduction The cause of alopecia universalis has not been confirmed. However, it has been known from clinical observations that psy chological stress may be associated with this disease [1] and recent studies suggest the cause may be related to immunological ab normality [2], Since a study of psychoneuro immunology (PNI) has connected psycho logical stress and immunological abnormal ity [3], we treated cases of alopecia univer salis according to the mechanism of PNI. in which the mental effect modulates the im mune functions, using a therapy combining psychotherapy and an immunosuppressant, and obtained favorable results. We would like to call this combined therapy ‘psychoim
munotherapy’. Psychotherapy was com bined with relaxation (autogenic training, AT) [4] and image therapy [5], and small doses of immunosuppressant (prednisolone and ciclosporin, CYA) were used as chemo therapy. In combination with psycho therapy, small doses of immunosuppressant were efficacious without side effects. In order to clarify the effect of psycho therapy in this disease, two groups (one with psychotherpay and immunotherapy and another with immunotherapy) were com pared. and the comparison demonstrated that the psychotherapy group produced a more effective result. The efficacy was immunologically studied through the variation in peripheral immune cells, mainly lympho cytes. When blood flow in and temperature
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Abstract. Mental stress and immunological abnormality have recently been listed as causes of alopecia universalis. This disease is difficult to treat with only ordinary pharma cotherapy. Thus, from the standpoint of psychoneuroimmunology, stress was relieved by relaxation and image therapy, and administration of small doses of a strong immunosuppres sant was effective, leading to clinically favorable results. In addition, changes were recog nized in the subpopulation of peripheral lymphocytes and in p-endorphin before and after relaxation and image therapy. The treatment of alopecia universalis favorably changed the subpopulations of T cells. A patient suffering from alopecia is always under stress. Alleviat ing this stress facilitates recovery of immunological competence. Our method was effective in 5 of 6 cases with refractory alopecia universalis.
236
Teshima/Sogawa/Mizobe/Kuroki/Nakagawa
fable I . Cases of alopecia universalis Case
Sex
Age
Onset
1 2 3 4 5 6 7 8 9 10 11
M F M M T M M F M F F
16 17 19 19 28 19 9 28 9 11 24
15 10 14 14 18 5 5 24 2 8 22
Atopic
+
+
+ +
Psychosocial incidence
Psycho therapy
Hair growth
rearrange class separation from teacher rearrange class entrance examination new employment unknown traffic accident love affair, abortion unknown rearrange class new' employment
+ + + + + +
+ + + + + -
-
+
-
-
-
-
-
-
Mean age: 18.1 ± 6.4: 19.6 ± 3.9 (cases 1-6), 16.2 ± 8.1 (cases 7-11).
Materials and Methods Patients The subjects were 11 patients with refractory alo pecia universalis. Table I presents the age, sex, dura tion of the disease and psychosocial incidence which are assumed to be the causes of hair loss. Immuno therapy was given to these 11 alopecia universalis patients. Psychotherapy was added in 6 patients (cases 1-6). Only chemotherapy was given to 5 pa tients (cases 7-11). There was no significant differ-
encc in age, sex and duration of the disease between the two groups. Psychoimmunotherapy Psychotherapy was initiated concomitantly with chemotherapy. As for chemotherapy, prednisolone 510 mg/day was first administered orally for 2 months alone and subsequently with CYA (2.5 mg/kg). Before the patients agreed to the administration of CYA, they were given sufficient information about the ef fects and side effects of CYA from their attending physicians. To prevent side effects, blood examina tions for kidney and liver function were carried out every month. As for weekly psychotherapy, relaxation and image therapy were conducted for 30 min once a week. After sufficient relaxation by AT as a relaxation therapy, image therapy was introduced, having the patients visualize and repeat the image to themselves that ‘the hair root cells become healthy by receiving nutrients from the rich blood flow at their alopecia lesion’, that ‘all head hair grows’, and that *1 am very self-confident’. In order to enhance ‘image therapy’, the patients drew their own cured image which they actually imagined at the end of the image therapy, using a marker pen and drawing paper. Immunological Examinations The influence of psychoimmunotherapy on the immune cells of peripheral blood was investigated.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
at the scalp and variation in immune cells in peripheral blood were investigated before and after relaxation and image therapy, re laxation and image therapy proved to in fluence the physiologic variation in the scalp and immune cells. Thus, psychotherapy and immunosuppressant chemotherapy, which are complementary, are considered to effec tively enhance the action of the immune sys tem in alopecia universalis. The results con firmed the importance of the immune func tion in the pathological condition of this dis ease.
Psychoimmunotherapy in Alopecia
237
Table 2. Changes in lymphocytes subsets in the blood after psychoimmunotherapy (mean ± SE) Normal range
CD4. % CD8, % CD4/CD8 CD4+,D R \ % CD8* DR*. % IL-2R. % CD 16. % CD3. % CD24. %
42.1+7.6 33.4 + 6.6 1.3 ±0.4 1.0 ±0.9 2.9±3.8 8.0± 1.2 30.6 ± 10.7 69.1 ± 10.5 11.0±4.0
Group A (n = 5)
Group B (n = 4)
before
after
before
after
39.2 ±2.7 27.5 ± 1.9 1.4 ±0.1 2.2±0.2 2.0±0.8 7.0 ± 1.3 13.2 ± 1.6 73.7±2.8 12.9 ± 2.0
36.6±2.4 33.0 ±2.1* 1.1 ±0.4* 1.6 ±0.2* 2.1 ±0.5 6.1 ±0.8 18.3± 1.8* 73.3 ±3.1 14.2 ± 1.5
45.4± 7.2 24.0± 3.8 1.9 ±0.3 2.9± 1.5 1.2 ±0.4 7.1 ±2.6 10.4± 1.5 77.4±4.0 10.3 ± 2.1
45.4 ± 1.4 29.9 ±2.4* 1.5 ± 0.2 2.1 ±0.7 1.6 ±0.4 6.3± 1.8 11.8 ±3.7 74.7 ± 3.2 11.6±0.7
*p < 0.05.
Investigation o f Effect o f Relaxation and linage Therapy Variations in subsets of lymphocytes and (5-endor phin in the peripheral blood of group A patients w'ere investigated before (‘A’ in table 3) and right after (*B" in table 3) the relaxation and image therapy 4 months after therapy w'as started. Before therapy, an injection needle, which was connected to the injector, was posi tioned in the arm. and after therapy sample blood was collected carefully so as not to cause pain to the patient. |3-Endorphin was measured using the RIAPEG method.
Table 3. Changes in lymphocyte subsets and level of |3-endorphin (mean ± SE) Normal range CD4. % CD8. % CD4/CD8 CD4* • DR‘. % CD8’ -DR’. % IL-2R. % CD 16. % CD3. % CD24. % P-Endorphin pg/ml
Before
42.1 ±7.6 39.9 ±2.6 33.4 ±6.6 32.8±2.9 1.3 ± 0.4 1.2 ±0.1 1.0 ± 0.9 1.1 ±0.1 2.9± 3.8 0.7 ±0.1 8.0± 1.2 6.2 ±0.6 30.6 ± 10.7 12.8 ± 1.9 69.1 ± 10.5 71.8 ± 3.4 11.0±4.0 14.0 ± 1.7 10 >
6.2±0.7
After
37.9 + 3.3 33.5 ±2.9 1.1 ±0.1 1.4 ±0.3 1.36 ±0.1* 7.2 ± 1.2 17.1 ±2.7* 70.7 ±2.5 13.1 ± 1.8 7.2± 1.2
*p < 0.05 (n = 5).
Blood flow and temperature at the scalp during the image therapy were measured by thermography (Thermovision-870, AGEMA. Japan), and laser Doppler rheometer (Peri Flux PF3. Perimed. Sweden) respectively. The terminal of the rheometer was set on the right side of the temporalis.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Sample blood was collected at 10 a.m. 1 day prior to the initiation of treatment. Four months later (2 months after CYA administration), sample blood af ter completion of the treatment was collected. Mainly examined were lymphocyte subsets. Lymphocyte subsets w'ere measured by flow cy tometry (Cytron: Ortho Diagnostic System, Inc., USA) with fluorescent monoclonal antibodies (Becton Dickinson. San José, Calif.. USA). The results were compared between the cases (group A: cases 1-5) by improved psychoimmuno therapy and the cases (group B: cases 8-11) not improved only by immunotherapy. There was no significant difference between the two groups in lymphocyte subsets before the treat ment (‘before' in table 2).
238
Teshima/Sogawa/Mizobe/Kuroki/Nakagawa
\ (b) therapy.
Statistics To statistically analyze the results in tables 2 and 3. levels before and after therapy were compared in a test of significant difference using the Wilcoxon method of nonparametric ANOVA. An actual level of less than 5% (p < 0.05) in the pair was regarded as a significant degree of difference (marked by one aster isk in tables 2 and 3).
Results Cases improved by this therapy included cases 1-5 and 7, whereas unimproved cases were cases 6, and 8-11 (table 1). In im proved cases, oral administration of CYA
and prednisolone was subsequently contin ued for 4-5 months. Even after the cessation of treatment in improved cases, hair has con tinued to grow for more than 6 months. Immunologic examinations showed changes in subsets of lymphocytes in the peripheral blood before and after therapy in groups A (cases 1-5) and B (cases 8-11; table 2). Statistically significant changes were found in CD8-positive T cells (active suppressor T-cells) in both groups and CD4/CD8 ratio, CD4-DR-positive T cells (active helper T cells) and CD 16-positive T cells (NK cells). All results of these cells changed to the normal range.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Kig. I. Case 4 before (a) and after
Psychoimmunotherapy in Alopecia
239
Fig. .3. Blood flow of the scalp measured by laser Doppler rheom eter during image therapy.
Changes in the p-endorphin level and population of immune cells in the peripheral blood were demonstrated before and after psychotherapy (table 3). Significant changes were found in the population of CDS-DRpositive T cells (active suppressor T cells) and CD 16-positive T cells (NK cell). Similar changes in CD 16-positive T cells (NK T cells) were found in the improved cases (group A in table 2). CD8- DR-positive T cells increased after psychotherapy. The levels of p-endorphin in peripheral blood were significantly elevated after relax ation and image therapy. Physical changes
during the image therapy in case 4 (fig. 1a. b) were measured by thermography (fig. 2) and laser Doppler rheometer (fig. 3). The tem perature of the scalp rose when the patient imagined 'My scalp has a rich blood flow and becomes warmer’. The blood flow also in creased during imagination. The (I) mark indicates the starting point of the imagina tion (fig. 3). This results showed an increase in the temperature of the scalp (‘post’, the right side in fig. 1) due to increased blood flow by the image therapy. The self-portrait drawn by the patients after each session of relaxation and image
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Fig. 4. Self-portrait drawn by the patient (case 4) at the early (a) and late stage (b) of psychoimmuno therapy.
therapy became more self-confident, if we compare the picture drawn at an advanced stage with that drawn at an early stage (fig. 4a, b). In 1 case (case 4), the patient hesitated to draw his own cured self-portrait at an early stage (fig. 4a). After being re leased from the stress by therapy, however, he could make a lively drawing without hesi tation (fig. 4b).
Discussion Treatment of alopecia universalis is diffi cult. Although all the cases were treated at departments of dermatology using various kinds of therapies including steroid therapy, concurrently in consultation with our de partment, no effect was seen. We thus treated these patients from the psychological and immunological perspectives with favor able results. While the causes are said to be associated with mental stress, this appears to rather intensify with the psychological condition after occurrence of the disease. In cases in which alopecia was displayed up to senior high school age. most patients, in fact, lacked close friendships and they stopped going to school. They rather aimlessly stayed at home regardless of the intensity of persuasion by parents, teachers in charge, friends or coun selors. However, when hair began to grow, they voluntarily returned to school. These facts indicate that it is necessary to treat these stress conditions as soon after occurrence of the disease as possible. It is important to remove tension due to stress and to make such patients gain selfconfidence through relaxation and image therapy.
The therapy was effective in 5 of 6 cases. The I noneffective case showed some find ings including one different from the other alopecia cases, for example, examination of the scalp tissue demonstrated no reaction of T cells at the periphery of the follicle regard less of epilation, so that a dermatologist sug gested a different cause. In the other cases, the immunofluorescent examinations of the tissue at epilation showed invasion by T cells at the periphery of the follicle, and the inva sion of T cells gradually disappeared in re sponse to the treatment. The effect of CYA on the central nerve opioid system is known [6], and relaxation and image therapy are related to this effect. When the effect of the image on immu nological competence was investigated, the change in endorphin was recognized, and changes in active suppressor T cells (CD8*'DR') and NK cells (CD 16) were also seen. Since (3-cndorphin is knwon to pro mote the activity of T cells in the peripheral blood [7], it may be strongly associated with the treatment of this disease, acting to com pensate for reduced activity of suppressor T cells and NK cells. As such, image therapy creates a physiological phenomenon which is advantageous in the treatment of alope cia. When physiological changes according to self-suggestion during image therapy were investigated, elevated dermal tempera ture and increased blood flow were recog nized. While one cause of alopecia is local circulatory failure [8], the blood flow of the scalp was reported to be increased by the imagery. A recent study of PNI proved that immunoreaction is affected by emotion [9], Epila tion in this disease occurs with some un derlying physical immunological abnormali ty. The patient is confused due to the change
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Teshima/Sogawa/Mizobe/Kuroki/Nakagawa
240
241
Psychoimmunotherapy in Alopecia
References 1 Beard HO: Social and psychological implications of alopecia areata, J. Am Acad Dermatol 1986; 14: 697-700. 2 Weert J De, Temmerman L, Kint A: Alopecia areata: A clinical study. Dermatológica 1984:168: 224-229. 3 Ader R: Psychoneuroimmunology. New York, Ac ademic Press. 1981. 4 I.uthe W: Autogenic Therapy. New York. Gruñe & Stratton. 1969.
5 Boysenko J: Minding the Body, Mending the Mind. Addison-Wesley 1987. 6 Dougherty PM, Dafny N: Cyclosporine affects central nervous system opioid activity via direct and indirect means. Brain Behav Immunol 1988; 2:242-253. 7 Wybran J. Appelbroom J, Famaey JP et al.: Sug gestive evidence for receptors for morphine and met-enkepalin on human blood T lymphocytes. J Immunol 1979;123:1068-1070. 8 Franchi mont CF. Pieard GE: Sebaceous glands of the scalp; in Orfanos, Montagna. Stuttgen (eds).: Hair Research. Berlin. Springer, 1981. pp 350352. 9 Locke SE, Gorman JR: in Kaplan HI, Sadock BJ (eds): The Comprehensive Textbook of Psychiatry/V, Baltimore. Williams & Wilkins. 1989.
Hideki Tcshima, MD Department of Psychosomatic Medicine Faculty of Medicine Kyushu University 3-1-1 Maidashi. Higashi-ku Fukuoka 812 (Japan)
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
in physical image with epilation and falls into a severe stress condition, so that he can not express himself in terms of his own healthy image. This stress is assumed to weaken severely the power to recover from his own immunological abnormality. Recov ery of immunocompetence is considered to be speeded by the recovery of a healthy selfimage in a relaxed condition.
© 1991 S. Kargcr AG. Basel 0033-3190/91/0564-02 35S2.75/0
Application of Psychoimmunotherapy in Patients with Alopecia universalis Hideki Teshima, Hiroshi Sogawa, Koji Mizobe, Naoko Kuroki, Tetsuya Nakagawa Department of Psychosomatic Medicine. Faculty of Medicine. Kyushu University. Fukuoka. Japan
Introduction The cause of alopecia universalis has not been confirmed. However, it has been known from clinical observations that psy chological stress may be associated with this disease [1] and recent studies suggest the cause may be related to immunological ab normality [2], Since a study of psychoneuro immunology (PNI) has connected psycho logical stress and immunological abnormal ity [3], we treated cases of alopecia univer salis according to the mechanism of PNI. in which the mental effect modulates the im mune functions, using a therapy combining psychotherapy and an immunosuppressant, and obtained favorable results. We would like to call this combined therapy ‘psychoim
munotherapy’. Psychotherapy was com bined with relaxation (autogenic training, AT) [4] and image therapy [5], and small doses of immunosuppressant (prednisolone and ciclosporin, CYA) were used as chemo therapy. In combination with psycho therapy, small doses of immunosuppressant were efficacious without side effects. In order to clarify the effect of psycho therapy in this disease, two groups (one with psychotherpay and immunotherapy and another with immunotherapy) were com pared. and the comparison demonstrated that the psychotherapy group produced a more effective result. The efficacy was immunologically studied through the variation in peripheral immune cells, mainly lympho cytes. When blood flow in and temperature
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Abstract. Mental stress and immunological abnormality have recently been listed as causes of alopecia universalis. This disease is difficult to treat with only ordinary pharma cotherapy. Thus, from the standpoint of psychoneuroimmunology, stress was relieved by relaxation and image therapy, and administration of small doses of a strong immunosuppres sant was effective, leading to clinically favorable results. In addition, changes were recog nized in the subpopulation of peripheral lymphocytes and in p-endorphin before and after relaxation and image therapy. The treatment of alopecia universalis favorably changed the subpopulations of T cells. A patient suffering from alopecia is always under stress. Alleviat ing this stress facilitates recovery of immunological competence. Our method was effective in 5 of 6 cases with refractory alopecia universalis.
236
Teshima/Sogawa/Mizobe/Kuroki/Nakagawa
fable I . Cases of alopecia universalis Case
Sex
Age
Onset
1 2 3 4 5 6 7 8 9 10 11
M F M M T M M F M F F
16 17 19 19 28 19 9 28 9 11 24
15 10 14 14 18 5 5 24 2 8 22
Atopic
+
+
+ +
Psychosocial incidence
Psycho therapy
Hair growth
rearrange class separation from teacher rearrange class entrance examination new employment unknown traffic accident love affair, abortion unknown rearrange class new' employment
+ + + + + +
+ + + + + -
-
+
-
-
-
-
-
-
Mean age: 18.1 ± 6.4: 19.6 ± 3.9 (cases 1-6), 16.2 ± 8.1 (cases 7-11).
Materials and Methods Patients The subjects were 11 patients with refractory alo pecia universalis. Table I presents the age, sex, dura tion of the disease and psychosocial incidence which are assumed to be the causes of hair loss. Immuno therapy was given to these 11 alopecia universalis patients. Psychotherapy was added in 6 patients (cases 1-6). Only chemotherapy was given to 5 pa tients (cases 7-11). There was no significant differ-
encc in age, sex and duration of the disease between the two groups. Psychoimmunotherapy Psychotherapy was initiated concomitantly with chemotherapy. As for chemotherapy, prednisolone 510 mg/day was first administered orally for 2 months alone and subsequently with CYA (2.5 mg/kg). Before the patients agreed to the administration of CYA, they were given sufficient information about the ef fects and side effects of CYA from their attending physicians. To prevent side effects, blood examina tions for kidney and liver function were carried out every month. As for weekly psychotherapy, relaxation and image therapy were conducted for 30 min once a week. After sufficient relaxation by AT as a relaxation therapy, image therapy was introduced, having the patients visualize and repeat the image to themselves that ‘the hair root cells become healthy by receiving nutrients from the rich blood flow at their alopecia lesion’, that ‘all head hair grows’, and that *1 am very self-confident’. In order to enhance ‘image therapy’, the patients drew their own cured image which they actually imagined at the end of the image therapy, using a marker pen and drawing paper. Immunological Examinations The influence of psychoimmunotherapy on the immune cells of peripheral blood was investigated.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
at the scalp and variation in immune cells in peripheral blood were investigated before and after relaxation and image therapy, re laxation and image therapy proved to in fluence the physiologic variation in the scalp and immune cells. Thus, psychotherapy and immunosuppressant chemotherapy, which are complementary, are considered to effec tively enhance the action of the immune sys tem in alopecia universalis. The results con firmed the importance of the immune func tion in the pathological condition of this dis ease.
Psychoimmunotherapy in Alopecia
237
Table 2. Changes in lymphocytes subsets in the blood after psychoimmunotherapy (mean ± SE) Normal range
CD4. % CD8, % CD4/CD8 CD4+,D R \ % CD8* DR*. % IL-2R. % CD 16. % CD3. % CD24. %
42.1+7.6 33.4 + 6.6 1.3 ±0.4 1.0 ±0.9 2.9±3.8 8.0± 1.2 30.6 ± 10.7 69.1 ± 10.5 11.0±4.0
Group A (n = 5)
Group B (n = 4)
before
after
before
after
39.2 ±2.7 27.5 ± 1.9 1.4 ±0.1 2.2±0.2 2.0±0.8 7.0 ± 1.3 13.2 ± 1.6 73.7±2.8 12.9 ± 2.0
36.6±2.4 33.0 ±2.1* 1.1 ±0.4* 1.6 ±0.2* 2.1 ±0.5 6.1 ±0.8 18.3± 1.8* 73.3 ±3.1 14.2 ± 1.5
45.4± 7.2 24.0± 3.8 1.9 ±0.3 2.9± 1.5 1.2 ±0.4 7.1 ±2.6 10.4± 1.5 77.4±4.0 10.3 ± 2.1
45.4 ± 1.4 29.9 ±2.4* 1.5 ± 0.2 2.1 ±0.7 1.6 ±0.4 6.3± 1.8 11.8 ±3.7 74.7 ± 3.2 11.6±0.7
*p < 0.05.
Investigation o f Effect o f Relaxation and linage Therapy Variations in subsets of lymphocytes and (5-endor phin in the peripheral blood of group A patients w'ere investigated before (‘A’ in table 3) and right after (*B" in table 3) the relaxation and image therapy 4 months after therapy w'as started. Before therapy, an injection needle, which was connected to the injector, was posi tioned in the arm. and after therapy sample blood was collected carefully so as not to cause pain to the patient. |3-Endorphin was measured using the RIAPEG method.
Table 3. Changes in lymphocyte subsets and level of |3-endorphin (mean ± SE) Normal range CD4. % CD8. % CD4/CD8 CD4* • DR‘. % CD8’ -DR’. % IL-2R. % CD 16. % CD3. % CD24. % P-Endorphin pg/ml
Before
42.1 ±7.6 39.9 ±2.6 33.4 ±6.6 32.8±2.9 1.3 ± 0.4 1.2 ±0.1 1.0 ± 0.9 1.1 ±0.1 2.9± 3.8 0.7 ±0.1 8.0± 1.2 6.2 ±0.6 30.6 ± 10.7 12.8 ± 1.9 69.1 ± 10.5 71.8 ± 3.4 11.0±4.0 14.0 ± 1.7 10 >
6.2±0.7
After
37.9 + 3.3 33.5 ±2.9 1.1 ±0.1 1.4 ±0.3 1.36 ±0.1* 7.2 ± 1.2 17.1 ±2.7* 70.7 ±2.5 13.1 ± 1.8 7.2± 1.2
*p < 0.05 (n = 5).
Blood flow and temperature at the scalp during the image therapy were measured by thermography (Thermovision-870, AGEMA. Japan), and laser Doppler rheometer (Peri Flux PF3. Perimed. Sweden) respectively. The terminal of the rheometer was set on the right side of the temporalis.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Sample blood was collected at 10 a.m. 1 day prior to the initiation of treatment. Four months later (2 months after CYA administration), sample blood af ter completion of the treatment was collected. Mainly examined were lymphocyte subsets. Lymphocyte subsets w'ere measured by flow cy tometry (Cytron: Ortho Diagnostic System, Inc., USA) with fluorescent monoclonal antibodies (Becton Dickinson. San José, Calif.. USA). The results were compared between the cases (group A: cases 1-5) by improved psychoimmuno therapy and the cases (group B: cases 8-11) not improved only by immunotherapy. There was no significant difference between the two groups in lymphocyte subsets before the treat ment (‘before' in table 2).
238
Teshima/Sogawa/Mizobe/Kuroki/Nakagawa
\ (b) therapy.
Statistics To statistically analyze the results in tables 2 and 3. levels before and after therapy were compared in a test of significant difference using the Wilcoxon method of nonparametric ANOVA. An actual level of less than 5% (p < 0.05) in the pair was regarded as a significant degree of difference (marked by one aster isk in tables 2 and 3).
Results Cases improved by this therapy included cases 1-5 and 7, whereas unimproved cases were cases 6, and 8-11 (table 1). In im proved cases, oral administration of CYA
and prednisolone was subsequently contin ued for 4-5 months. Even after the cessation of treatment in improved cases, hair has con tinued to grow for more than 6 months. Immunologic examinations showed changes in subsets of lymphocytes in the peripheral blood before and after therapy in groups A (cases 1-5) and B (cases 8-11; table 2). Statistically significant changes were found in CD8-positive T cells (active suppressor T-cells) in both groups and CD4/CD8 ratio, CD4-DR-positive T cells (active helper T cells) and CD 16-positive T cells (NK cells). All results of these cells changed to the normal range.
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Kig. I. Case 4 before (a) and after
Psychoimmunotherapy in Alopecia
239
Fig. .3. Blood flow of the scalp measured by laser Doppler rheom eter during image therapy.
Changes in the p-endorphin level and population of immune cells in the peripheral blood were demonstrated before and after psychotherapy (table 3). Significant changes were found in the population of CDS-DRpositive T cells (active suppressor T cells) and CD 16-positive T cells (NK cell). Similar changes in CD 16-positive T cells (NK T cells) were found in the improved cases (group A in table 2). CD8- DR-positive T cells increased after psychotherapy. The levels of p-endorphin in peripheral blood were significantly elevated after relax ation and image therapy. Physical changes
during the image therapy in case 4 (fig. 1a. b) were measured by thermography (fig. 2) and laser Doppler rheometer (fig. 3). The tem perature of the scalp rose when the patient imagined 'My scalp has a rich blood flow and becomes warmer’. The blood flow also in creased during imagination. The (I) mark indicates the starting point of the imagina tion (fig. 3). This results showed an increase in the temperature of the scalp (‘post’, the right side in fig. 1) due to increased blood flow by the image therapy. The self-portrait drawn by the patients after each session of relaxation and image
Downloaded by: King's College London 137.73.144.138 - 11/21/2017 6:02:57 AM
Fig. 4. Self-portrait drawn by the patient (case 4) at the early (a) and late stage (b) of psychoimmuno therapy.
therapy became more self-confident, if we compare the picture drawn at an advanced stage with that drawn at an early stage (fig. 4a, b). In 1 case (case 4), the patient hesitated to draw his own cured self-portrait at an early stage (fig. 4a). After being re leased from the stress by therapy, however, he could make a lively drawing without hesi tation (fig. 4b).
Discussion Treatment of alopecia universalis is diffi cult. Although all the cases were treated at departments of dermatology using various kinds of therapies including steroid therapy, concurrently in consultation with our de partment, no effect was seen. We thus treated these patients from the psychological and immunological perspectives with favor able results. While the causes are said to be associated with mental stress, this appears to rather intensify with the psychological condition after occurrence of the disease. In cases in which alopecia was displayed up to senior high school age. most patients, in fact, lacked close friendships and they stopped going to school. They rather aimlessly stayed at home regardless of the intensity of persuasion by parents, teachers in charge, friends or coun selors. However, when hair began to grow, they voluntarily returned to school. These facts indicate that it is necessary to treat these stress conditions as soon after occurrence of the disease as possible. It is important to remove tension due to stress and to make such patients gain selfconfidence through relaxation and image therapy.
The therapy was effective in 5 of 6 cases. The I noneffective case showed some find ings including one different from the other alopecia cases, for example, examination of the scalp tissue demonstrated no reaction of T cells at the periphery of the follicle regard less of epilation, so that a dermatologist sug gested a different cause. In the other cases, the immunofluorescent examinations of the tissue at epilation showed invasion by T cells at the periphery of the follicle, and the inva sion of T cells gradually disappeared in re sponse to the treatment. The effect of CYA on the central nerve opioid system is known [6], and relaxation and image therapy are related to this effect. When the effect of the image on immu nological competence was investigated, the change in endorphin was recognized, and changes in active suppressor T cells (CD8*'DR') and NK cells (CD 16) were also seen. Since (3-cndorphin is knwon to pro mote the activity of T cells in the peripheral blood [7], it may be strongly associated with the treatment of this disease, acting to com pensate for reduced activity of suppressor T cells and NK cells. As such, image therapy creates a physiological phenomenon which is advantageous in the treatment of alope cia. When physiological changes according to self-suggestion during image therapy were investigated, elevated dermal tempera ture and increased blood flow were recog nized. While one cause of alopecia is local circulatory failure [8], the blood flow of the scalp was reported to be increased by the imagery. A recent study of PNI proved that immunoreaction is affected by emotion [9], Epila tion in this disease occurs with some un derlying physical immunological abnormali ty. The patient is confused due to the change
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References 1 Beard HO: Social and psychological implications of alopecia areata, J. Am Acad Dermatol 1986; 14: 697-700. 2 Weert J De, Temmerman L, Kint A: Alopecia areata: A clinical study. Dermatológica 1984:168: 224-229. 3 Ader R: Psychoneuroimmunology. New York, Ac ademic Press. 1981. 4 I.uthe W: Autogenic Therapy. New York. Gruñe & Stratton. 1969.
5 Boysenko J: Minding the Body, Mending the Mind. Addison-Wesley 1987. 6 Dougherty PM, Dafny N: Cyclosporine affects central nervous system opioid activity via direct and indirect means. Brain Behav Immunol 1988; 2:242-253. 7 Wybran J. Appelbroom J, Famaey JP et al.: Sug gestive evidence for receptors for morphine and met-enkepalin on human blood T lymphocytes. J Immunol 1979;123:1068-1070. 8 Franchi mont CF. Pieard GE: Sebaceous glands of the scalp; in Orfanos, Montagna. Stuttgen (eds).: Hair Research. Berlin. Springer, 1981. pp 350352. 9 Locke SE, Gorman JR: in Kaplan HI, Sadock BJ (eds): The Comprehensive Textbook of Psychiatry/V, Baltimore. Williams & Wilkins. 1989.
Hideki Tcshima, MD Department of Psychosomatic Medicine Faculty of Medicine Kyushu University 3-1-1 Maidashi. Higashi-ku Fukuoka 812 (Japan)
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in physical image with epilation and falls into a severe stress condition, so that he can not express himself in terms of his own healthy image. This stress is assumed to weaken severely the power to recover from his own immunological abnormality. Recov ery of immunocompetence is considered to be speeded by the recovery of a healthy selfimage in a relaxed condition.
