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DOSE-RELATED VISUAL-FIELD DEFECTS IN PATIENTS RECEIVING PUVA THERAPY
1106 INTELLIGENCE TEST SCORES IN RELATION TO PARENTAL SOCIAL CLASS
selected controls from the same population. This reanalysis shows that only a small part of this difference in test scoring can be attributed to the association of obesity with low socioeconomic status. The finding of a cognitive deficiency in obesity raises the question whether it is a consequence of obesity or a manifestation of an underlying, common brain dysfunction of genetic or early environmental nature. We thank the Ministry of the Interior (psychological service of the Danish Armed Forces) for permission to use the draft board files. The study was supported by the Danish Heart Foundation.
Obesity Research Group, Department D 105, Herlev University Hospital, DK-1399 Copenhagen K, Denmark
THORKILD I. A. SØRENSEN STIG SONNE-HOLM UFFE CHRISTENSEN
DOSE-RELATED VISUAL-FIELD DEFECTS IN PATIENTS RECEIVING PUVA THERAPY
SIR,-The use of oral 8-methoxypsoralen and subsequent to longwave ultraviolet light (PUVA) is a widely accepted
exposure
treatment
for
psoriasis and other
skin disorders.
Eye protection
is
provided during and after therapy to prevent cataracts and photokeratitis. Visual-field defects have not to our knowledge been reported in association with PUVA. However, we have seen transient visual-field defects in three patients during- PUVA treatment, the defects appearing to be dose related. Case 1.-A 50-year-old woman with a 35-year history of psoriasis was put on PUVA in June, 1978. In December, 1981, when the dosage of 8-methoxypsoralen was increased to 40 mg twice weekly, and photophobia developed, with a central scotoma which lasted up to 20 min before disappearing to the left of her visual field. These attacks occurred about three times daily at first, but when the dose was reduced to 20 mg twice weekly the frequency of the attacks fell to about twice weekly. Only occasional attacks occurred on 20 mg weekly, and she remains symptom-free on 10 mg weekly. These episodes are reproducible on challenge with an increase in psoralen nausea
dosage.
Case2.-A 25-year-old woman who had had psoriasis since 4 years was put on PUVA therapy in March, 1982. When the 8-methoxypsoralen dosage was increased to 30 mg twice weekly, nausea developed associated with a sudden pain in her right eye and tunnel vision affecting both eyes. The episodes lasted up to 5 min. No symptoms occurred on 20 mg psoralen weekly but recurred on increasing the dose to 30 mg weekly. She has a history of migraine. Case 3. -A 65-year-old man with a 35-year history of psoriasis was put on PUVA in 1978. Nausea and tunnel vision developed 30-60 min after taking 40 mg of 8-methoxypsoralen; the symptoms lasted for about 8 h and cleared when treatment stopped. of age
Although there has always been some concern about potential damage to the eyes during PUVA therapy, few ocular side-effects have been reported. Keratitis may occur if patients neglect to wear their goggles and cataract formation has been induced in animals treated with PUVA for a long time with very high psoralen dosage.1,2 There are no reports of cataracts in patients with vitiligo TM, Hakim R, Griffin AC. Photosensitization of the eye with methoxsalen. Arch Ophthalmol 1960, 64: 346-51 2. Cloud TM, Hakim R, Griffin AC. Photosensitization of the eye with methoxsalen II. Arch Ophthalmol 1961; 66: 689-94. 1. Cloud
treated with long-term PUVA—indeed, several reports confirm the absence of cataract formation in patients on PUVA.3,4 A mild form of photokeratoconjunctivitis may occur in some patients on PUVA, manifest by photophobia, irritation, conjunctivitis, and dry eyes.5 The tear break-up time may also be significantly reduced by returns to normal after treatment. Although visual-field defects have not previously been reported in association with oral 8-methoxypsoralen and ultraviolet A, the fact that we have seen three patients out of a total of sixty-six patients treated with PUVA therapy, suggests that there may be other patients elsewhere who have experienced minor dose related visualfield defects whilst on treatment. All three patients were examined by ophthalmologists both before and after treatment (and following episodes of visual disturbance) and no abnormality was found. Department of Dermatology, Wycombe General Hospital, High Wycombe, Bucks HP1 1 2TT
DAVID A. FENTON
JOHN D. WILKINSON
LANGERHANS CELL DEPLETED ALLOGRAFT SKIN ON EXCISED BURNS
SIR,-The need for resurfacing large areas of the body on a burned patient with allograft split skin frequently arises when not enough autograft skin is available to treat a large burn. This "biological dressing" will diminish the loss of fluids, electrolytes, and proteins, and pain and bacterial infections, and will enhance the wellbeing of the patient. However, the allograft skin is rejected within 2 weeks because of incompatibility between donor and recipient tissue type. The human epidermis harbours a population of cells (Langerhans cells6) which are of bone-marrow origin.7 They reach the skin via the blood and migrate to the epidermis where their role is thought to be immunological. All nucleus-containing cells express HLA A, B, C antigens (class I) on their surface which are recognised by allogeneic T-lymphocytes. In human skin keratinocytes express this antigen system. The Langerhans cells also express class n antigens (ie, homologues of Ia for mouse and HLA-D/Dr for man)8,9 which can stimulate allogeneic T-lymphocytes. HLA-D/Dr antigens may activate allogeneic T-lymphocytes which in turn attack HLA A, B, C-expressing cells, here the keratinocytes of the allograft. To weaken this rejection mechanism we have reduced the number of Langerhans cells in allograft split skin by ultraviolet B radiation before putting the skin on the patient. We were able to remove more than 90% of Langerhans cells as demonstrated by ATP-ase staining. We have tried Langerhans cell depleted skin in one burned patient and in three patients with crural ulcers. In the burned patient the skin (1255 x 1255 cm) has taken, with no signs of rejection (by day 62). In the three patients with crural ulcers the skin has also taken and is in a well-healed state (days 62, 54, and 46). We believe that by interfering with the afferent pathway of the immune reaction we can diminish the immunological reaction against the transplantation antigens of the donor type. We are now trying to enhance the removal of Langerhans cells from allograft split skin and investigating the physiology of such transplanted skin. Department of Plastic Surgery and Burns Unit, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark
BJARNE F. ALSBJÖRN
3. Back O, Hollström E, Liden S, Thorburn W. Absence of cataract ten years after treatment with 8-methoxypsoralen. Acta Dermatovener (Stockh) 1980; 60: 79-80. 4. El-Mofty AM, EI-Mofty A. Retrospective ocular study of patients receiving oral 8-methoxypsoralen and solar irradiation for the treatment of vitiligo. Ann Ophthalmol 1979; 11: 946-48. 5. Backman HA The effects of PUVA on the eye. Am J Optom Physiol Optics 1982; 59: 86-89 6. Langerhans P. Über die Nerven der menschlichen Haut. Virchows Arch Pathol Anat 1868; 44: 325. 7. Katz SI, Kunihiko T, Sachs DH. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 1979; 282: 324-26. 8. Rowden G, Lewis MG, Sullivan AK. Ia antigen expression on human epidermal Langerhans cells. Nature 1977; 268: 247-48 9. Klareskog L, Tjernlund UM, Forsum U, Peterson PA. Epidermal Langerhans cells express Ia antigens. Nature 1977; 268: 248-50.
selected controls from the same population. This reanalysis shows that only a small part of this difference in test scoring can be attributed to the association of obesity with low socioeconomic status. The finding of a cognitive deficiency in obesity raises the question whether it is a consequence of obesity or a manifestation of an underlying, common brain dysfunction of genetic or early environmental nature. We thank the Ministry of the Interior (psychological service of the Danish Armed Forces) for permission to use the draft board files. The study was supported by the Danish Heart Foundation.
Obesity Research Group, Department D 105, Herlev University Hospital, DK-1399 Copenhagen K, Denmark
THORKILD I. A. SØRENSEN STIG SONNE-HOLM UFFE CHRISTENSEN
DOSE-RELATED VISUAL-FIELD DEFECTS IN PATIENTS RECEIVING PUVA THERAPY
SIR,-The use of oral 8-methoxypsoralen and subsequent to longwave ultraviolet light (PUVA) is a widely accepted
exposure
treatment
for
psoriasis and other
skin disorders.
Eye protection
is
provided during and after therapy to prevent cataracts and photokeratitis. Visual-field defects have not to our knowledge been reported in association with PUVA. However, we have seen transient visual-field defects in three patients during- PUVA treatment, the defects appearing to be dose related. Case 1.-A 50-year-old woman with a 35-year history of psoriasis was put on PUVA in June, 1978. In December, 1981, when the dosage of 8-methoxypsoralen was increased to 40 mg twice weekly, and photophobia developed, with a central scotoma which lasted up to 20 min before disappearing to the left of her visual field. These attacks occurred about three times daily at first, but when the dose was reduced to 20 mg twice weekly the frequency of the attacks fell to about twice weekly. Only occasional attacks occurred on 20 mg weekly, and she remains symptom-free on 10 mg weekly. These episodes are reproducible on challenge with an increase in psoralen nausea
dosage.
Case2.-A 25-year-old woman who had had psoriasis since 4 years was put on PUVA therapy in March, 1982. When the 8-methoxypsoralen dosage was increased to 30 mg twice weekly, nausea developed associated with a sudden pain in her right eye and tunnel vision affecting both eyes. The episodes lasted up to 5 min. No symptoms occurred on 20 mg psoralen weekly but recurred on increasing the dose to 30 mg weekly. She has a history of migraine. Case 3. -A 65-year-old man with a 35-year history of psoriasis was put on PUVA in 1978. Nausea and tunnel vision developed 30-60 min after taking 40 mg of 8-methoxypsoralen; the symptoms lasted for about 8 h and cleared when treatment stopped. of age
Although there has always been some concern about potential damage to the eyes during PUVA therapy, few ocular side-effects have been reported. Keratitis may occur if patients neglect to wear their goggles and cataract formation has been induced in animals treated with PUVA for a long time with very high psoralen dosage.1,2 There are no reports of cataracts in patients with vitiligo TM, Hakim R, Griffin AC. Photosensitization of the eye with methoxsalen. Arch Ophthalmol 1960, 64: 346-51 2. Cloud TM, Hakim R, Griffin AC. Photosensitization of the eye with methoxsalen II. Arch Ophthalmol 1961; 66: 689-94. 1. Cloud
treated with long-term PUVA—indeed, several reports confirm the absence of cataract formation in patients on PUVA.3,4 A mild form of photokeratoconjunctivitis may occur in some patients on PUVA, manifest by photophobia, irritation, conjunctivitis, and dry eyes.5 The tear break-up time may also be significantly reduced by returns to normal after treatment. Although visual-field defects have not previously been reported in association with oral 8-methoxypsoralen and ultraviolet A, the fact that we have seen three patients out of a total of sixty-six patients treated with PUVA therapy, suggests that there may be other patients elsewhere who have experienced minor dose related visualfield defects whilst on treatment. All three patients were examined by ophthalmologists both before and after treatment (and following episodes of visual disturbance) and no abnormality was found. Department of Dermatology, Wycombe General Hospital, High Wycombe, Bucks HP1 1 2TT
DAVID A. FENTON
JOHN D. WILKINSON
LANGERHANS CELL DEPLETED ALLOGRAFT SKIN ON EXCISED BURNS
SIR,-The need for resurfacing large areas of the body on a burned patient with allograft split skin frequently arises when not enough autograft skin is available to treat a large burn. This "biological dressing" will diminish the loss of fluids, electrolytes, and proteins, and pain and bacterial infections, and will enhance the wellbeing of the patient. However, the allograft skin is rejected within 2 weeks because of incompatibility between donor and recipient tissue type. The human epidermis harbours a population of cells (Langerhans cells6) which are of bone-marrow origin.7 They reach the skin via the blood and migrate to the epidermis where their role is thought to be immunological. All nucleus-containing cells express HLA A, B, C antigens (class I) on their surface which are recognised by allogeneic T-lymphocytes. In human skin keratinocytes express this antigen system. The Langerhans cells also express class n antigens (ie, homologues of Ia for mouse and HLA-D/Dr for man)8,9 which can stimulate allogeneic T-lymphocytes. HLA-D/Dr antigens may activate allogeneic T-lymphocytes which in turn attack HLA A, B, C-expressing cells, here the keratinocytes of the allograft. To weaken this rejection mechanism we have reduced the number of Langerhans cells in allograft split skin by ultraviolet B radiation before putting the skin on the patient. We were able to remove more than 90% of Langerhans cells as demonstrated by ATP-ase staining. We have tried Langerhans cell depleted skin in one burned patient and in three patients with crural ulcers. In the burned patient the skin (1255 x 1255 cm) has taken, with no signs of rejection (by day 62). In the three patients with crural ulcers the skin has also taken and is in a well-healed state (days 62, 54, and 46). We believe that by interfering with the afferent pathway of the immune reaction we can diminish the immunological reaction against the transplantation antigens of the donor type. We are now trying to enhance the removal of Langerhans cells from allograft split skin and investigating the physiology of such transplanted skin. Department of Plastic Surgery and Burns Unit, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark
BJARNE F. ALSBJÖRN
3. Back O, Hollström E, Liden S, Thorburn W. Absence of cataract ten years after treatment with 8-methoxypsoralen. Acta Dermatovener (Stockh) 1980; 60: 79-80. 4. El-Mofty AM, EI-Mofty A. Retrospective ocular study of patients receiving oral 8-methoxypsoralen and solar irradiation for the treatment of vitiligo. Ann Ophthalmol 1979; 11: 946-48. 5. Backman HA The effects of PUVA on the eye. Am J Optom Physiol Optics 1982; 59: 86-89 6. Langerhans P. Über die Nerven der menschlichen Haut. Virchows Arch Pathol Anat 1868; 44: 325. 7. Katz SI, Kunihiko T, Sachs DH. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 1979; 282: 324-26. 8. Rowden G, Lewis MG, Sullivan AK. Ia antigen expression on human epidermal Langerhans cells. Nature 1977; 268: 247-48 9. Klareskog L, Tjernlund UM, Forsum U, Peterson PA. Epidermal Langerhans cells express Ia antigens. Nature 1977; 268: 248-50.