Volume 94, Number 2, February 1976
`
`British Journal of
`
`Dermatology
`
`Published for the
`
`British Association of Dermatologists
`
`by Blackwell Scientific Publications
`
`Oxford London Edinburgh Melbourne
`
`ISSN ooo7 0963
`This mate rial was tnpied
`atthe NLI-.11 and may be
`Su bjett U5 Cc:-pigright Laws
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`British Journal of Dermatology, Volume 94, Number 2, February 1976
`
`CONTENTS
`
`W-G5
`119
`
`123
`
`I3 I
`
`..
`
`..
`
`Clinical and Laboratory Investigations
`Langerhans Cells in the Epidermis of Athymic Mice
`_
`_
`J’. A. A. HUNTER, D. ]. FAIRLEY, G. G. PRIESTLEY AND H. A. CUBI
`Necrotizing Vasculitisz a Circulating Immune Complex Producing Inflammatory Skin Lesions
`I
`1. VERRIER JONES, R. H. CUMMING, c. M. ASPLIN, R. R. M. IIARMAN AND C. R._ TRIBE
`.
`A Comparison of I-listocompatibility Antigens in Dermatitis Herpetiformis and Adult Coeliac Disease
`I’. P. SIEAH, LIoNEL I-‘RY, 1. w. KEARNEY, ELIZABETH CAMPBELL, J. F. MOWBRAY, J. s. STEWART AND A. v.
`IJOFFBRAND
`_
`_
`,
`.
`Histocompatibility Antigens and Dermatitis Herpctiformis with Special Reference to Jejunal Abnormalities
`and Acetylator Phenotype
`....,-
`.
`_
`T. REUNALA, 0. 1’. SALO, A. TIILIKAINEN AND M. J. MATTILA
`The Action of a Urea—Lactic Acid Ointment in Ichthyosis: with Particular Reference to the Thickness of the
`Horny Layer
`CICELY BLAIR
`Skin Lesions in Human Yersiniosis. A Histopathological and lmmunohistological Study
`i<iRsTI—MARIA NIEMI, MATTI HANNUKSELA AND OSMO P. SALO
`Skin Surface Lipid Composition in Rosacea
`R. 1. PYE, GAY MEYRICK AND J. L. BURTON
`Sebaceous Lipogenesis in Human Skin. Variability with Age and with Severity of Acne
`MARY F. COOPER, HELEN MCGRATII AND SAM SHUS‘l‘h'R
`Lymphocyte Abnormalities in Mycosis Fungoides
`RONA MACKIE, F. R. SLESS, REEECCA COCIIRAN AND MARIA DE SOUSA
`International Mortality from Bullous Diseases since I950
`J. A. SAVIN
`
`......
`
`Pharmacology and Treatment
`A New Model for Human Bioassay of Topical Corticosteroids
`E. s. N. REDDY AND GURMOHAN SINGH
`The Inhibiting Effect of Soft Paraffin on the Kobner Response in Psoriasis
`1. s. COMAISII AND I. s. GREENER
`
`Case Reports
`......
`......
`Cutaneous Alternariosis
`N. BANG PEDERSEN, P.—A. MARDH, T. HALLBERG AND N. JONSSON
`Atypical lclithyosiform Erythroderma, Deafness and Keratitis. A Report of Two Cases
`R. 1. G. RYCROI-‘T, L’. J. MOYNAIIAN AND R. s. WELLS
`Brief Communications
`
`Acid Hydrolases in Psoriatic Epidermis
`P. D. MIER AND 103).’: J. M. A. VAN DEN IIURR
`Mycosis Fungoides: Model for T—1ymphocyte Homing to the Skin?
`M. GOOS,
`I<AIsr.RLING AND K. LENNERT
`Review
`Tropical Dermatology. Cutaneous Leislunaniasis
`A. BRYCESON
`
`Society Proceedings
`South West of England and Wales Dermatological Society
`Book Reviews
`
`News and Notices
`
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`

`
`British Journal of Dermatology
`
`EDITOR
`
`DR R. H. CHAMPION
`Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ
`
`EDITORIAL ADVISORY BOARD
`
`PROF. B.E.D.COOKE, Cardiff
`Oral Medicine
`
`PROF. I.A.MAGNUS, London
`Photobiology
`
`DR C.N.D.CRUICKSHANK, Birmingham
`Experimental pathology
`
`PROF. MARY MARPLE S, Woodstock
`Microbiology
`
`PROF. F.] .EBLING, Sheffield
`Zoology
`
`DR ].C.GENTLES, Glasgow
`Mycology
`
`DR W.E .PARI S H, Sharnbrook
`Experimental pathology
`
`DR A.C.STEVENSON, Oxford
`Genetics
`
`MR _T.W.I-IADGRAFT, Cambridge
`Pharmacy
`
`PROF. ].L.TURK, London
`Immunology
`
`PROF. HERMANN LEHMANN, Cambridge
`Biochemistry
`
`MR G.S.\X/ALTON, Liverpool
`Comparative dermatology
`
`ASSISTANT EDITORS
`
`DR P.W.M.COPEMAN, London
`
`DR ].N.S.MITCHELL, Royal Air Force
`
`DR RONALD MARKS, Cardiff
`
`DR W.C.NOBLE, London
`
`DR P.D.MIER, Nijmegen
`
`DR R.S.WELLS, London
`
`EDITOR OF SOCIETY PROCEEDINGS
`
`DR I.N.S.MITCHELL,
`40 Meadow Way, Letchworth, Herts.
`
`British fournal of Dermatology is published monthly. Subscription price
`£21.00 U.K. (overseas £25.00; U.S.A. and Canada $75.00) per annum, post
`free. Subscriptions should be addressed to Blackwell Scientific Publications
`Ltd, Osney Mead, Oxford OX2 GEL, England.
`
`Printed in Great Britain at the Alden Press, Oxford
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`
`Dermatologica
`
`Offiziellcs Organ dcr Schweizcrischen Gcsellschaft fiir Dermatologie und Venerologie
`Official Organ of the Nederlandse Vereniging van Dermatologen
`Official Organ of the Belgian Society for Dermatology and Syphiligraphy
`
`Managing Editor: R. Schuppli (Basel) Editors: G. Achten (Bruxelles) J. Delacrétaz (Lausanne)
`L.H. Jansen (Utrecht)A. Kint (Gent) C.M. Lapiére (Liege) J. W. Mali (Nijmegen) M.K. Polano
`(Leiden) U.W. Schnyder (Heidelberg)
`
`Index Vol. 150, No.6, 1975
`
`Omar, A. and Krebs, A. (Bcrnc): Mode of Dermal-Epidermal Adhesion
`Ishikawa, H. and Horiuchi, R, (Maebashi): Initial Change ofGIycosaminoglycans in Systemic
`Sclcroderma
`
`Fusaro, R.M. and Johnson, J.A. (Omaha, Nebr.): Protection against Long Ultraviolet and/
`or Visible Light with Topical Dihydroxyacetone. Implications for the Mechanism
`of Action of the Sunscreen Combination, Dihydroxyacetone/Naplithoquinone
`Young, E. andLeun, J C. van der (Utrecht): Treatment of Psoriasis with Long~Wave Ultraviolet
`Light
`
`Mittal, Radha: Handa, PI, and Sharma, S.C. (Patiala): Incontinentia Pigmenti et Achromians
`Chorzelski, T.; Jablonska. Stefania; Maciejowska, Ewa, and Blaszczyk. Maria (Warsaw):
`Visken as Supplementary Drug in the Treatment of Pemphigus
`(Montreal): Generalized Mastocytosis, Relapsing Herpes Zoster and Polyradi—
`culoneuritis
`
`Kalz, F.
`
`Bersaques, J. de (Gent): Vitamin A Acid in the Topic Treatment of Plantar Warts
`
`The Interesting Case ~ Der interessante Fall - Un cas intéressant
`Staak, W.J.B.M. van de: Cotton, D. W.K.,' Jonckheer—Venneste, M.M.}1., and Boerbooms,
`A.M. TIH. (Nijmcgcn): Lichenoid Eruption Following Penicillamine. A Case Report
`with some Biochemical Observations
`
`Varia
`Subject Index
`Author Index
`Index Vol. 150
`
`Subscriptiondata: ‘Dermatologica’ appears monthly in numbersofapproximately
`64 pages each. 6 numbers form 1 volume and 2 volumes are issued annually.
`Subscription price per volume SFI. 110.— / US $ 50.00
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`S. Karger - Basel - Munchen - Paris - London - New York - Sydney
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`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Britislzjournal of Dermatology (1976) 94, 195.
`
`The inhibiting effect of soft paraflin on the
`
`Kobner response in psoriasis
`
`].S.COMAISH AND ].S.GREENER
`
`Department of Dermatology, Royal Victoria Infirmary, Newcastle-upon-Tyne NEI 4LP
`
`Accepted for publication 2 June 1975
`
`SUMMARY
`
`White soft paraffin has been shown to inhibit the development of the isomorphic response (Kobner
`phenomenon) in psoriasis. The possible reasons for this are discussed and it is suggested that this
`finding has implications which should lead to a greater understanding of the nature of psoriasis.
`
`Despite intense efforts throughout the world the causation of psoriasis remains a bafliing problem
`(Shuster, I97I). Two main facts seem fundamental—that genetic factors play an important role
`(Watson, Cann & Farber, 1972), and that certain trigger factors may provoke the psoriatic reaction
`in the individual so constituted. Trigger factors may be systemic, e.g. streptococcal infections (Whyte
`& Baughman, 1964) or local, such as physical injury. The latter is often called the Kobner or iso-
`morphic response, and is clinically and histologically indistinguishable from spontaneous lesions,
`apart from its shape, which closely follows the area traumatized. Classically it follows 6-I8 clays
`after injury, which may be a scratch, sunburn, abrasion or operation wound. It has been shown that
`both epidermis and dermis must be damaged before the reaction occurs (Stankler, 1969). Since there
`is no animal model of psoriasis, the Kobner effect provides the only controllable method currently
`available for research into this common disorder. Consequently it has been extensively investigated
`with regard to the type, degree and depth of injury producing it, the time course between stimulus
`and response and the appearances at the clinical, histological and electron microscopical level. Many
`chemicals and drugs have been used in attempts to suppress the reaction, without success. It is
`obvious that if a method were available to prevent or suppress the reaction, it would be of the greatest
`possible significance, botl1 theoretically and at the clinical level where it might well prove a source of
`practical techniques in the management of the spontaneous disease.
`A positive response indicates active disease, and multiple simultaneous stimuli anywhere on the
`skin produce an equal number of responses (Pedace, Muller & Winkelmann, 1969). This observation
`is of great significance and accords well with observations suggesting that psoriasis is latent throughout
`the whole integument even when only localized plaques are visible clinically.
`The following experiments were designed to test the hypothesis that a positive Kobner reaction is
`due to local overgrowth of bacterial organisms (especially streptococci) at the site of trauma. If this
`were so it would correlate well with the guttate psoriasis reactions seen after systemic strepotoeoccal
`I95
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`I96
`
`_7. S.Comaz'sh and ].S. Greener
`
`infections, the individual lesions here being produced possibly by streptococcal products released into
`the blood stream and settling in the skin. As will be seen, the results do not support this hypothesis
`at all, but instead show that soft paraffin used as an ointment base has a significant inhibiting effect on
`the Kébner response.
`
`MATERIALS AND METHODS
`
`Subjects
`These were I04 adult patients with active psoriasis who had given their informed consent to the
`procedures used. Patients receiving antibiotics, sulphonamides or antimitotics (e.g. methotrexate or
`hydroxyurea) were not included. Routine topical therapy was given, avoiding the test areas of skin.
`Neobacrin ointment (Glaxo) containing 5 mg of neomycin and 500 units bacitraein zinc in each
`gram of paraflin base was supplied in tubes identical to those containing only the base. These
`preparations were coded and the key kept by the pharmacy staff. The stimulus consisted of a short
`(I cm approx.) single scratch or cross made with a sterile needle on the upper outer arm or back.
`The response was read at 7, I4 and 21 days usually, but this varied according to the individual
`patient’s convenience. The greatest response in each scratch was then read as negative, doubtful
`(P) or positive (+, + +, or + + +) and these were scored as 0, 0-5, I, 2, 3 respectively.
`Five sets of experiments were done:
`(I) Nine subjects were tested on one site only and the scratch lesion was cultured for bacterial organ-
`isms on the 1st, 3rd and 7th day after stimulus (day 0).
`(2) Sixteen patients were tested on both upper outer arms and one of these sites after scratching
`was treated with Neobacrin ointment twice daily for 3 weeks, the other side being left untreated. The
`results were read blind, that is, without the observer being aware which side had been treated.
`(3) Eighteen patients were tested as in (2) but one side was treated with Neobacrin ointment and
`the other with its base again twice daily for 3 weeks, using a double—blind system.
`(4) Thirty-one patients were tested as in (3) but with an additional stimulus over the back, which
`was left untreated. The results were read ‘blind’ as in (2) above.
`(5) Thirty patients were tested as in (2) but the base was used instead of Neobacrin ointment, the
`other side being left untreated. The results were read ‘blind’ as in (2).
`
`RESULTS
`
`The data have been analysed using ‘the sign test’ for non-parametric observations.
`
`Experiment I
`None of the lesions gave positive cultures for pathogenic organisms. Eight of the nine patients gave a
`positive Kébner reaction.
`
`Experiment 2 (Table 1)
`Seven of the sixteen patients gave positive reactions, all on the untreated side. These results show a
`significant inhibitory effect of Neobacrin compared with the untreated sites (P = 0006 using a two-
`tailed test).
`
`Experiment 3 (Table 2)
`Four of the eighteen patients tested gave positive reactions as follows:
`Control side (ointment base), 4 ; Neobacrin side, 3.
`There is no significant difference between Neobacrin ointment and its base in these experiments.
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`I97
`Eflect of soft paraflin on the Kélmer response in psoriasis
`TABLE 1. Effect of Neobacrin ointment on the
`TABLE 2. Comparison of Neobacrin and its base on the
`Kiibner response in sixteen patients
`Kiibnet response in eighteen patients
`
`Untreated site
`
`Neobacrin treated site
`
`Site treated with base
`
`Site treated with Neobacrin
`
`Negative (14)
`
`+ .
`
`1,
`+
`
`Negative (14)
`
`Comment: no significant difference between Neobacrin
`and its base.
`
`Y
`
`1, yulvT‘ITTi‘'7‘ _i_
`.v+,
`iv*‘.‘“r'V|I
`
`Scoring system: negative — : 0; doubtful (P)
`= o-5;positive + = 1-0; +—}— = 20; +++
`= 3-0.
`Results: two-tailed sign test gives 1) = 0-006
`indicating Neobacrin has a significant effect on
`the Kéibner response.
`
`Experiment 4 (Table 3)
`These results confirm that there is no significant difference between the eilect of Neobacrin and that
`of its base on the Kobner response, and that Neobacrin inhibits the response compared with untreated
`sites. Additionally it is shown that the ointment base itself has a significantly inhibitory effect on the
`Kobncr reaction. Table 4 shows that this effect is of approximately the same degree as that of the
`Neobacrin ointment.
`
`Experiment 5 (Table 4)
`These results confirm the previous findings of Experiment 3 (Table 4) that the base inhibits the
`Kobnet response.
`
`DISCUSSION
`
`This series of experiments gave unexpected results but it is possible that these are more significant
`than those looked for would have been. It is clear that the ointment base—soft parafl"1n—has a sub-
`stantial inhibiting effect on the Kobner response, which in many cases prevented the reaction com-
`pletely. We have considered a number of possible explanations.
`I. Epidermal hydration. It is known that soft pataflin increases the hydration of epidermis and that
`this is also one of the chief eifects of polythene occlusion (Anderson et al., 1973). The latter tends to
`decrease mitotic rate and produce partial resolution of the psoriatic plaques. Since our own work was
`begun it has been reported that simple ointment bases may also decrease mitotic rate and labelling
`index in stimulated mouse epidermis (Tree & Marks, 1974). The common mechanism of epidermal
`hydration may be significant in all of these and our own observations.
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`j’. S.Comaish and j‘. S.Greener
`
`TABLE 3. Comparison of effect on Kfibner response in
`thirty-one patients of (a) Neobacrin (b) base (c) no
`treatment
`:
`
`Site treated
`with Neobacrin
`
`Site treated
`with Ease
`
`Untreated site
`
`Negative (14)
`—
`
`Negative (14)
`—
`
`Negative (I4)
`+
`
`Scoring system: see Table 1.
`Results: (1) Since Neobaerin previously shown to inhibit
`Kéibner response, can use one-tailed test which gives
`P = 002 indicating Ncobacrin significantly inhibited
`Kobner response, confirming previous experiment. (2)
`There is no significant difference between Neobacrin
`and its base, confirming previous experiment. (3) Using
`a one—tailed test, base significantly inhibited Kobner
`response, P = o‘o35.
`
`2. Bacterial hindrance. Inunction of a greasy ointment base may physically entrap bacteria which
`would otherwise invade and multiply in damaged tissue. This supposes that bacteria do play a role in
`the Ktibner response; one would have expected in this case some discernible difference between the
`inert base and base plus a powerful combination of antibiotics, which is certainly not apparent in the
`present data.
`3. Oxygen lack. An impermeable layer of parafiin might prevent ready access of molecular oxygen
`to a rapidly metabolizing tissue (Hammer & Hellerstrom, 1968). This implies a requirement for and
`ability to utilize atmospheric molecular oxygen by damaged epidermis.
`4. Retention of mitosis inhibitors. The sealing effect of paraflin might reduce or prevent loss of
`chalone or some such mitosis inhibitor. Its absorption back into the dividing zone of the epidermis
`could be enhanced by increased hydration as in (1) above.
`5. Specific chemical effect. There could be a direct chemical effect of the soft paraffin—-or some
`component—on the psoriatic process.
`We believe that whatever the ultimate explanation, this observation has far—ranging implications
`which might provide a springboard for further advances in the field of psoriatic research.
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`
`Eflect of soft parafiin on the Kiilmer response in psoriasis
`
`I99
`
`TABLE 4. Comparison of Kobner
`response in untreated sites and sites
`treated with base only in thirty patients
`
`Untreated control
`site
`
`Treated site
`(base only)
`
`_[-
`
`TA BLE 5. Overall scores for Kobner responses for all
`sites tested
`
`Ncobacrin — I9 out of 65 tested
`Base
`- 25-5 out of 79 tested
`Untreated -— 44 out of 77 tested
`
`29-2%
`323%
`571%
`
`Scoring System: see Table I.
`Results: One-tailed test gives P =
`0-018 indicating that the base signifi-
`cantly inhibited Kobner response.
`
`ACKNOWLEDGMENTS
`
`We wish to thank Miss L. Wilson of Messrs. Glaxo for supplies of Neobacrin ointment and its base,
`and Mr R. Elder and Mrs A. Saunders of the hospital pharmacy for help with the organization of the
`trials. Mrs D. Wcightman gave valuable statistical advice.
`
`ANDERSON, R.L., CASSIDY, J.M., HANSEN, JR. 8: YELLIN, W. (1973) The effect of in viva occlusion on human
`stratum corneum hydration-dehydration in tuitro. _7ourual of Investigative Dermatology, 61, 375.
`
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`
`].S.Comaz'sh and _?'.SGreener
`
`HAMMER, H. 8: HELLERSTROM, C. (1968) Oxygen consumption of the germinal epithelium in psoriatie human skin
`as measured by the Cartesian diver micro-gasometer. Acta dermato-vcnerealagica, 48, 563.
`PEDACE, F.]’., MULLER, S.A. & WINKELMANN, R.I(. (1969) Biology of psoriasis: experimental study of the Kobner
`phenomenon. Aura derma£0—'Uene1'e0logica, 49, 390.
`Sx—1UsTI5t<, S. (x971) Research into psoriasis—the last decade. British Medical journal, iii, 236.
`STANKLER, L. (1969) An experimental investigation on the site of skin damage inducing the Kiibncr reaction in
`psoriasis. British ffaztrnal of Dermatology, 81, 534.
`TREE, S. & MARKS, R. (1974) An explanation for the ‘placebo’ effect of bland ointment bases. British journal of
`Dermatology, 92, 195.
`WATSON, \X/., CANN, I—I.M. & FARBER, E.M. (I972) The genetics of psoriasis. Archives of Dermazalog , 105, I97.
`WI—IYTE, H.J. & BAUGHMAN, R.D. (1964) Acute guttate psoriasis and streptococcal infection. Archives of Derm-
`alolog v, 89, 3 50.
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