British Joumal of Dermatology (1977) 97, 279.

Light sensitivity in mycosis fungoides G.VOLDEN AND P.O.THUNE Department of Dermatology, Rikshospitalet, Oslo, Norway Accepted for publication 25 February 1977

SUMMARY

Because of suspected photosensitivity, twelve patients suffering from mycosis fungoides have been phototested with various wavebands. Four patients experienced a burning sensation and erythema following sun-exposure, after the disease had progressed to stage II. On phototesting, abnormal reactions were observed in 7 patients. The offending wavebands were situated mostly in the UVA range, but also in the UVB range and in visible light.

Mycosis fungoides (MF) is generally regarded as a malignant lymphoma always appearing first in the skin. The disease has classically been divided into three stages (premycotic, infiltrative and tumour stages). It can affect the skin for a period varying from a few months up to 30 years before affecting the lymph nodes and internal organs. Studies of peripheral blood and lymph nodes have brought some evidence that the neoplastic cells are thymus-derived (T) lymphocytes. The aetiology of the disease is unknown. Many patients, however, relate its appearance to a drug or an allergic reaction, and an allergic component can often be identified. Tan et al. (1974) supported the hypothesis that MF is a chronic granulomatous response to persistent unidentified antigen(s), upon which immune imbalance can develop resulting in 'auto-immune' phenomena, and in a few cases leading to the emergence of various lymphoreticular neoplasms. Light sensitivity in MF has drawn very little attention, and since one MF patient with lightsensitivity appeared at our clinic about i year ago, we have discovered by phototesting that several cases may have pathological light-reactions. During the last year we have collected and phototested 12 MF patients. The results are compared with the data obtained in 22 normal subjects.

MATERIALS AND METHODS

Twelve patients were investigated, all having a clinical history and appearance typical for MF. The diagnosis was verified histologically in all patients. The group consisted of 5 women and 7 men aged 42-78 years, the average being 61 years. Nine of them were classified in stage II (plaques or infiltration) and three in stage III (tumours) (Table i). All had normal routine haematological and histochemical tests. Four patients had a history of reactions to sunlight and experienced pruritus and dermatitis on exposed areas. 279

28o

G. Volden and P.O.Thme TABLE I. Sex, age distribution and stage of disease in 12 patients with mycosis fungoides Case I* 2*

3 4 5 6 7* 8 9 10* II 12

Patient

Sex

Age

MF-stage

R.O. E.S. M.H. R.P. A.S.

F F

II

M M F

59 57 68

E.J. J.H.

F M

A.L. 0.0. O.A. M.T. F.F.

M

II III

M F

42

II II III II II II II III

M

78

II

M

50

57 69 54 56 63 78

* Anamnestically sensitive to sunlight.

Gase I. R.O., female, aged 59 years, housewife, brunette. From 1973 she had had widespread erythematous spots on the body and extremities. From January 1975 increasing infiltrated plaques appeared, especially on the upper part of the body and on the upper limbs. The diagnosis MF stage II was confirmed both clinically and histologically in August 1975. During the summer of 1975 she noticed a slightly desquamating dermatitis on sun-exposed areas, and also slight itching and burning on the rest of the body. Gase 1. E.S., female, aged 57 years, innkeeper, blond. Previously she had been healthy. From the beginning of 1974, intermittent erythema and eczematous lesions developed over her body. From April 1975 the lesions on the body increased to infiltrated plaques the size of a child's hand. The diagnosis MF stage II was confirmed both clinically and histologically in August 1975. During the summer of 1975 she noticed burning and erythema on the face after sun-exposure. She had never sunbathed very much and had not previously experienced direct discomfort. Gase 7. J.H., male, aged 54 years, industrial worker. He had had pulmonary tuberculosis in 1950, and since then no sign of relapse. He had been an alcoholic for some years, but for the last 3 years a teetotaller. From i960 intermittent psoriasis-like skin lesions had appeared on his body. From January 1975 increasing infiltrated plaques, up to 7-8 cm in diameter, had been present on his body and lower limbs. The diagnosis MF stage II was confirmed both clinically and histologically in June 1976. During the summer of 1976, he noticed itching and a burning feeling, accompanied by erjthema and slight oedema, on sun-exposed areas after sun-bathing. Gase 10. O.A., male, aged 78 years, retired manager. Intermittently from 1963 he had noticed erythematous areas on his body, at first interpreted as seborrhoeic eczema. From 1973 abundant widespread coin-sized infiltrated plaques appeared on his body, and also a few on the extremities. He had always sunburned easily, but in the last 2-3 years he had been even more sensitive and developed erythema on sun-exposed areas accompanied by itching and burning. On examination in September 1976, he had a well-defined erythema on his face and the backs of his hands.

Light sensitivity in mycosis fungoides 0,99

281

WG320

S

GG /^95 I 561

XKGI

« 0.50 ,§ 0,10 0,01

\ 300

iOO

500

600

700

800

Wavelength (nm)

FIGURE I. Transmittance of the individual filters as measured spectrophotometrically.

Twenty-two subjects, males and females, aged 17-54 years, served as controls and were tested in the same way as the patients. Light testing procedure

Normal skin (size of radiated area = 10 mm diameter) was phototested with an Osram High Pressure Xenon Arc Lamp (XBO = 150 W) without any mirror or lens focussing system and equipped with different Schott filters. The lamp was placed at a distance of 20 cm from the patient's skin. All tests were performed on the back. Energy output was measured prior to each exposure with a Hewlett & Packard Radiant Flux Meter. Transmission characteristics were measured spectrophotometrically (Fig. i). The following filters were used: KGi-f3io (interference filter), half bandwidth (h.bw.) 305-315 nm and tenth bandwidth (t.bw.) 301-317 nm; KGi + WG 320, h. bw. 345-745 nm; KGi + WG 320-fUG 5 (i.e. UVA) h.bw. 350-390 nm, KG, -I-405 (interference filter), h.bw. 397-412 nm and t.bw. 391-417 nm; KGj-l-GG 495 h.bw. 495-745 nm; KG,-F561 (interference filter) h.bw. 535-585 nm and t.bw. 518-597 nm. Thickness of the cut-off filters was: KG], 2 nun; WG 320,3 mm; UG5, 2 mm; GG 495, 2 mm. The mean dose rate (or irradiance) at 20 cm from the unfiltered Xenon Arc Lamp was 210 mW.cm"^. The KG; filter was used mainly to reduce heat from the strong lines in Xenon emission at 800-1000 nm. The range of exposure times used for the different filter combinations was approximately: KG, + 310, 20-200 s; KG,-t-WG 320, 30-360 s; KG,-I-WG 320-I-UG5, 10-40 min; KG,-1-405, 10-30 min; KG, -I-GG 495, 5-15 min; KG, -h561, 10-30 min.

20 en

tj 3 u>

o d

10 5

80 200

5000 10000

15000

20000 25000 30000 35000

Dose (m j . cnn-2) '—' Filter KG + 310; • Filter KG+WGJM ; -Filter KG+WG,jo+UGs(UVA), FIGURE 2. M i n i m a l erythema dose ( M E D ) in 22 normal subjects (doses in m j c m

G.Volden and P.O.Thune

282

The typical irradiance with the Xenon Arc Lamp read with the Hewlett-Packard Meter for each filter combination was approximately: KG1-I-31OJ 1-2 mW.cm"^; KGi-l-WG 320, 130 KG,-fWG 320-1-UG5, 9 mW.cm"^; KG, 4-405, 0-5 mW.cm"^; KG,-1-GG 495, 80 KG14-561, 5mW.cm-^ The dose which gave a faint but distinct erythema, minimum erythemal dose (MED) and an apparent threshold papular response (PR) were recorded at 8, 24 and 48 h after irradiation. RESULTS

Controls Fig. 2 shows the doses corresponding to the MED obtained in 22 normal subjects. With the KGi -I- 310 nm interference filter combination all 22 subjects reacted with erythema after doses of 80-200 mj.cm"^. With the KGj-l-WG 320 filter and 11-36 J.cm"^ erythema occurred in nine normals, TABLE 2. Abnormal reactions (MED and PR) in patients with mycosis fungoides (doses in mj.cm ~^) Filters Case

KGi

MED

-I-310 PR

I 2

3 4 5 6 7 8 9 10 II 12

KG14-WG320 MED

PR

MED

PR

9000 8400

18000 16800

12600 12600

DNI DNI

16800

13500

DNI

19200 18000

15300

DNI

DNI

(21600)

6o

120

8400

60

DNI

(14000)

30

90

KGi-fWG32O-H UG 5

9000 (15600)

DNI

KG,-1-GG495

K G , L+405

MED

PR

DNI

60000

DNI

DNI

25200

DNI

MED

PR

900

900

•'

14400

DNI

DNI = Dose not increased. The figures in parentheses are considered normal, but are included to show the relation with the other wavelengths to which the patients reacted abnormally. Cases 3, 5, 6, 11 and 12 showed no abnormal reactions.

whereas the others did not react to 36 J.cm"^. In the UVA spectrum (KG, -I-WG 320-I-UG5 filters) 5 had reactions from doses of 16 8-260 J.cm"^, while the others did not react to the highest dose tested, i.e. 26 J.cm"^. With all the above mentioned filter combinations the erythema was delayed and appeared at 8 hours or later. Thus it was interpreted as probably a non-thermal response. None of the controls showed a papular response. No reactions were obtained with wavelengths above 400 nm using the different filter combinations mentioned above. Patients Table 2 shows the MED and the PR considered to be pathological in MF patients in relation to the normal controls. Three patients had pathological reactions with the KGj -t-310 filter: 30-60 mj.cm"^; five patients reacted pathologically with the KG, -f WG filter: 84-9-0 (19-2 PR) J.cm"^; five patients

Light sensitivity in mycosis fungoides

283

had pathological reactions with K G I - F W G - | - U G 5 filter: i2-6-i5-3 J.cm"^; while two patients had erythema to visible light and this can be considered an abnormal reaction (Cases 4 and 7). When the test dose was increased by ca. 100% above the MED (Table 2) in five patients, they all showed a papular reaction, in addition to the one who reacted with a papular reaction to the original dose. In total 7 of 12 MF patients had pathological light sensitivity and in 6 of the 7, PR occurred when the test dose was doubled. The 7th patient developed the PR without increased dosage. Two patients (Nos 4 and 10) showed a papular reaction with irradiation through the KGj -I-310 nm interference filter combination to doses of 90-120 mj.cm"^. Such a response was never seen in the controls. The MEDs of 3 patients (nos 4, 7 and 10) were from 30-60 mj.cm"^ which dose range was below that found in normals. With the KGi -I- WG 320 filters 5 patients (nos i, 2,4,8 and 9) showed a papular response at i6-8-i9-2 J.cm"^. Again this response was not seen in the control subjects. It may be noted that one patient (No. 8) reacted with a papular response but not with erythema alone. But 4 others reacted with erythema to smaller doses than that causing a papular response and had MEDs of 8-4-9 o J.cm"^. This MED range is again just below that found in the normals. With the filter combination giving UVA, 4 patients (nos i, 2, 4 and 8) had MEDs of I2-6-I5-3 J.cm"'^, which were also just below the values found in those normals that reacted to this part of the spectrum. Another patient (No. 9) showed a papular response to UVA. Two patients (Nos 4 and 7) reacted to visible light with erythema, whereas none of the controls did so. Although we were not able to test all patients to all filter combinations and give doses above the observed MEDs, it may be noted that 6 patients developed papular responses on irradiation at one part or another of the spearum, in most instances with doses 2-3 times above their MED. Thus, 7 of 12 MF patients had some evidence suggestive of abnormal photosensitivity, in 6 because of a pathological morphological response, in i (No. 7) because of the development of erythema to visible light with doses that were without action in normals. In conclusion we noticed that approximately 40% of the MF patients had an action spectrum involving UVA and in a minor degree UVB and visible light. The small number of patients must, however, be taken into account. DISCUSSION

The investigation of patients with light sensitivity is intended to determine whether they respond to light of an appropriate wavelength in a manner which differs from normal. From the small group presented here, it is likely that many patients with MF suffer from photosensitivity over a wide wavelength range. Light sensitivity in MF has previously drawn very little attention. Ive (1964) reported one case, and Van Scott & Yu (1975) described another case with associated photosensitivity in which phototests confirmed his markedly low threshold erythema dose for both UVA and UVC in normal skin. Kobori et al. (1974) described 5 actinic mycosis fungoides cases, and by using monochromatic irradiation tests found that an erythematous reaction was easily provoked in the UV-area 310-350 nm. It seems very likely that these patients represented actinic reticuloid rather than MF. Several authors have described photosensitivity in diseases related to MF. Wiskemann (1965) reported a case of light provokable granulomatous reticulosis. Jensen & Sneddon (1970) described a case of actinic reticuloid which was associated with reticulum cell sarcoma. It has been recognized for many years that patients with cutaneous lymphocytomata may show evidence of associated photosensitivity. Frain-Bell & Magnus (1971) reported two cases of cutaneous lymphocytomata associated with solar urticaria and polymorphic light eruption. Phototesting results suggested that the action spectrum in each case was probably dependent on the type of associated photodermatosis and not on the lymphocytoma. Lutzner (1975) has indicated that Sezary's syndrome, which is closely related to

284

G. Volden and P.O. Thune

j most often begins on the face, and that the skin sometimes develops infiltrated lesions. These usually occur on the face, but do not mean that light is necessarily associated with the disease, even if it may seem suspicious. The four MF patients with light sensitivity stated that they reacted abnormally to light only after being classified in stage II. None of these padents appeared to have been exposed to photoactive substances, or to have suffered from systemic disease, other than MF, or its treatment. There was no clear history of photodermatosis in these 12 padents, except in one case. This patient described sharply defined erythema on sun-exposed areas, while 3 others developed only faint and less definable erythema and a burning sensation on sun-exposed areas. Nevertheless, there had been a clear provocation by sunlight. The last 3 patients could hardly define the time relationship between sunexposure and the subsequent skin reaction. All 4 patients got worse during the most sunny months, but they did not notice anything abnormal in the winter. By systematic phototesting of these MF patients, independent of a history of light sensitivity, we discovered in about one half of them a decreased MED over a wide acdon spectrum involving UVB, UVA and visible wavelengths, with most pathological reactions in the longwave UV-area. Even if the MED was just below normal, clearly pathological reactions such as PR were obtained in a high percentage at all UV wavelengths when the exposure was increased to double the MED. We do not know the reason for light sensitivity in MF, but it was striking that the patients did not develop abnormal responses until the disease had reached stage IL Knowing that it is not possible histopathologically to find abnormal cells before stage II, one might think these cells to be entirely or partly responsible for the light sensitivity in MF. Presumably these reactions involve some mediator system which also functions abnormally in apparently normal skin, since all tests were performed on unaffected areas. Even without coming closer to the pathogenesis, we think that MF and actinic reticuloid (AR) have many striking features in common clinically, histologically and photobiologically. Both diseases start in a similar manner as a non-specific dermatitis, even if the light factor is considerably more apparent in AR than in MF. The diseases differ in that AR does not develop lymphomas even if the histologieal picture of the skin may resemble a lymphoma with abnormal cells from the lymphocyte series. Also in AR the patients react more strongly to longer wavelengths, such as visible light. Even if the photobiological results of this study are by no means conclusive, they indicate a relationship between mycosis fungoides and light sensitivity. REFERENCES BURG, G . & BRAUN-FALCO, O. (1975) Classification and differentiation of cutaneous lymphomas. British Journai of Dermatology, 93, 597. FRAIN-BELL, W . & MAGNUS, I.A. (1971) A study of the photosensitivity factor in cutaneous lymphocytoma. British Journal of Dermatology, 84, 25. IvE, F.A. (1964) Mycosis fungoides presenting as light sensitivity. British Journal of Dermatology, 76, 145. JENSEN, N . E . & SNEDDON, l.B. (1970) Actinic reticuloid with lymphoma. Birtish Journal of Dermatology, 82, 287. KoBORi, T., ToDA, K., ARAKI, H . , IKEMURA, I., YosHil, T. & HASEGAWA, K . (1974) Actinic mycosis fungoides. In: Sunlight and Man (Ed. by T.B.Fitzpatrick, M.A.Pathak, L.C.Harber, M.Seiji and A.Kukita), p. 703. University of Tokyo Press, Japan. LuTZNER, M., EDELSON, R . , SCHEIN, P . . GREEN, I., KIRKPATRICK, C . & AHMED, A. (1975) Cutaneous T-cell

lymphomas: the S6zary syndrome, mycosis fungoides, and related disorders. Annals of Internal Medicine, 83, 534TAN, R . S - H . , BUTTERWORTH, C M . , MCLAUGHLIN, H . , MALKA, S. & SAMMAN, P . D . (1974) Mycosis fungoides—a

disease of antigen persistence. British Journal of Dermatology, 91, 607. VAN SCOTT, E.J. & Yu, R.J. (1975) Melanogenesis from topical mechlorethamine and analogues in skin of hairless mice and in vitiligo. Journal of Investigative Dermatology, 64, 476. WiSKEMANN, A. (1965) Lichtprovozierbare granulomatose Reticulose. Dermatologische Wochenschrift, 151, 1420.

Light sensitivity in mycosis fungoides.

British Joumal of Dermatology (1977) 97, 279. Light sensitivity in mycosis fungoides G.VOLDEN AND P.O.THUNE Department of Dermatology, Rikshospitalet...
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