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Page 1: DOSE-RELATED VISUAL-FIELD DEFECTS IN PATIENTS RECEIVING PUVA THERAPY

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INTELLIGENCE TEST SCORES IN RELATION TO

PARENTAL SOCIAL CLASS

selected controls from the same population. This reanalysis showsthat only a small part of this difference in test scoring can beattributed to the association of obesity with low socioeconomicstatus. The finding of a cognitive deficiency in obesity raises thequestion whether it is a consequence of obesity or a manifestationof an underlying, common brain dysfunction of genetic or earlyenvironmental nature.

We thank the Ministry of the Interior (psychological service of the DanishArmed Forces) for permission to use the draft board files. The study wassupported by the Danish Heart Foundation.

Obesity Research Group,Department D 105,Herlev University Hospital,DK-1399 Copenhagen K, Denmark

THORKILD I. A. SØRENSENSTIG SONNE-HOLMUFFE CHRISTENSEN

DOSE-RELATED VISUAL-FIELD DEFECTS INPATIENTS RECEIVING PUVA THERAPY

SIR,-The use of oral 8-methoxypsoralen and subsequentexposure to longwave ultraviolet light (PUVA) is a widely acceptedtreatment for psoriasis and other skin disorders. Eye protection isprovided during and after therapy to prevent cataracts and

photokeratitis. Visual-field defects have not to our knowledge beenreported in association with PUVA. However, we have seentransient visual-field defects in three patients during- PUVAtreatment, the defects appearing to be dose related.

Case 1.-A 50-year-old woman with a 35-year history of psoriasiswas put on PUVA in June, 1978. In December, 1981, when thedosage of 8-methoxypsoralen was increased to 40 mg twice weekly,nausea and photophobia developed, with a central scotoma whichlasted up to 20 min before disappearing to the left of her visual field.These attacks occurred about three times daily at first, but when thedose was reduced to 20 mg twice weekly the frequency of the attacksfell to about twice weekly. Only occasional attacks occurred on 20mg weekly, and she remains symptom-free on 10 mg weekly. Theseepisodes are reproducible on challenge with an increase in psoralendosage.Case2.-A 25-year-old woman who had had psoriasis since 4 years

of age was put on PUVA therapy in March, 1982. When the8-methoxypsoralen dosage was increased to 30 mg twice weekly,nausea developed associated with a sudden pain in her right eye andtunnel vision affecting both eyes. The episodes lasted up to 5 min.No symptoms occurred on 20 mg psoralen weekly but recurred onincreasing 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 wasput on PUVA in 1978. Nausea and tunnel vision developed 30-60min after taking 40 mg of 8-methoxypsoralen; the symptoms lastedfor about 8 h and cleared when treatment stopped.Although there has always been some concern about potential

damage to the eyes during PUVA therapy, few ocular side-effectshave been reported. Keratitis may occur if patients neglect to weartheir goggles and cataract formation has been induced in animalstreated with PUVA for a long time with very high psoralendosage. 1,2 There are no reports of cataracts in patients with vitiligo

1. Cloud 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.

treated with long-term PUVA—indeed, several reports confirm theabsence of cataract formation in patients on PUVA.3,4 A mild formof photokeratoconjunctivitis may occur in some patients on PUVA,manifest by photophobia, irritation, conjunctivitis, and dry eyes.5The tear break-up time may also be significantly reduced by returnsto normal after treatment.

Although visual-field defects have not previously been reported inassociation with oral 8-methoxypsoralen and ultraviolet A, the factthat we have seen three patients out of a total of sixty-six patientstreated with PUVA therapy, suggests that there may be otherpatients elsewhere who have experienced minor dose related visual-field defects whilst on treatment.

All three patients were examined by ophthalmologists both beforeand after treatment (and following episodes of visual disturbance)and no abnormality was found.

Department of Dermatology,Wycombe General Hospital,High Wycombe, Bucks HP11 2TT

DAVID A. FENTON

JOHN D. WILKINSON

LANGERHANS CELL DEPLETED ALLOGRAFT SKINON EXCISED BURNS

SIR,-The need for resurfacing large areas of the body on a burnedpatient with allograft split skin frequently arises when not enoughautograft skin is available to treat a large burn. This "biologicaldressing" will diminish the loss of fluids, electrolytes, and proteins,and pain and bacterial infections, and will enhance the wellbeing ofthe patient. However, the allograft skin is rejected within 2 weeksbecause 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 viathe blood and migrate to the epidermis where their role is thought tobe immunological. All nucleus-containing cells express HLA A, B,C antigens (class I) on their surface which are recognised byallogeneic T-lymphocytes. In human skin keratinocytes express thisantigen system. The Langerhans cells also express class n antigens(ie, homologues of Ia for mouse and HLA-D/Dr for man)8,9 whichcan stimulate allogeneic T-lymphocytes. HLA-D/Dr antigens mayactivate allogeneic T-lymphocytes which in turn attack HLA A, B,C-expressing cells, here the keratinocytes of the allograft. Toweaken this rejection mechanism we have reduced the number ofLangerhans cells in allograft split skin by ultraviolet B radiationbefore putting the skin on the patient. We were able to remove morethan 90% of Langerhans cells as demonstrated by ATP-ase staining.We have tried Langerhans cell depleted skin in one burned patientand in three patients with crural ulcers. In the burned patient theskin (12 5 5 x 12 5 5 cm) has taken, with no signs of rejection (by day62). In the three patients with crural ulcers the skin has also takenand 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 reactionagainst the transplantation antigens of the donor type. We are nowtrying to enhance the removal of Langerhans cells from allograftsplit skin and investigating the physiology of such transplanted skin.

Department of Plastic Surgeryand 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 aftertreatment with 8-methoxypsoralen. Acta Dermatovener (Stockh) 1980; 60: 79-80.

4. El-Mofty AM, EI-Mofty A. Retrospective ocular study of patients receiving oral8-methoxypsoralen and solar irradiation for the treatment of vitiligo. AnnOphthalmol 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 Anat1868; 44: 325.

7. Katz SI, Kunihiko T, Sachs DH. Epidermal Langerhans cells are derived from cellsoriginating in bone marrow. Nature 1979; 282: 324-26.

8. Rowden G, Lewis MG, Sullivan AK. Ia antigen expression on human epidermalLangerhans cells. Nature 1977; 268: 247-48

9. Klareskog L, Tjernlund UM, Forsum U, Peterson PA. Epidermal Langerhans cellsexpress Ia antigens. Nature 1977; 268: 248-50.