British Journal of Dermatology (1979) iOO, 599.
Society Pvoceedin^s
Proceedings of the 213th Meeting of the Netherlands' Society of Dermatologists^ Nijmegen, 27 May 1978 PRESIDENT: DR M.J.WOERDEMAN HOST: PROF. DR J.W.H.MALI SUMMARIES OF PAPERS Treatment of psoriasis with ultraviolet-B light J.BOER, A.A.SCHOTHORST AND D.SUUBMOND
Department of Dermatology, University Hospital, Leiden, The Netherlands The efFect of ultraviolet-B light was investigated in fifteen patients with long-standing, widespread, and stable psoriasis. Patients whose skin lesions had invariably shown considerable improvement (at least 90",,) after consistent exposure to sunlight, usually in combination with seabathing, were selected for this treatment. Irradiation was provided by twelve 122 cm Philips TL 12 40 W fluorescent tubes and twelve 61 cm 20 W tubes mounted on two hinged upright frames. These lamps emit a continuous wavelength spectrum ranging from approximately 280 to 380 nm with a peak at 305 nm. At a height of 80 cm from the floor, the irradiance was 3-1 mW/cm'at a distance of 50 cm from the panel and i-5mW/cm-at 100 cm. Betore treatment was started, light tests were carried out with the light panel to determine the MED on the back and a lower leg for the wavelength spectrum from 280 to 380 nm. The first therapeutic light dose administered was equal to the sub-MED. In almost all of the patients the sub-MED was found to be definitely lower for the back than for the legs. Consequently, in most cases additional irradiation was given to the lower legs and the elbows during the treatment. The dosages were gradually increased by 20-40",, per session, depending on the increasing skin tolerance. During the initial phase (clearing phase) four irradiations a week were given. An effort was made to keep the longest exposure time for each side of the body below 30 min during the initial phase and below 10 min during the maintenance phase. Thirteen of the fifteen patients showed an improvement amounting to between 80 and 100",, relative to the pretreatment condition. The initial phase required an average of twenty-three irradiations. In the maintenance phase, twelve of the fifteen patients showed an improvement of So-ioo','« on a schedule of one irradiation every 1-5 weeks. The high therapeutic scores may, in our opinion, be attributed to one or more of three factors: the selection of patients, the type of light source, and the method of irradiation. Acrodermatitis and the foot-pump function J.P.KuiPER,
A.J.M.BRAKKEE AND J.J.COLLARD
Department of Dermatology, University of Nijmegen In t965, Mali & Kuiper described the syndrome of acroangiodcrmatits (A.A.D.), so-called pseudoKaposi, considering it as a peculiar manifestation of chronic venous insufficiency (C.V.I.) and suggesting 0OO7-O963/79/05oo-0599$O2.oo Ci t979 British Association of Dermatologists 599
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that in these patients in addition to incompetence of the calf muscle piunp the venous foot-pump action is particularly impaired. Kuiper (1966) gave some quantitative information about this foot-pump activity. Using a non-invasive method of venous pressure determination (Kuiper & van de Staak, 1970) quantitative data can more easily be obtained. The venous pressure fail was measured following active movement of foot and leg and following passive movement by kneading the foot with both hands. The measurements were performed at three different levels—the big toe, the middle of the foot and just above the ankle region—in a group of normal volunteers, a group of patients suffering from C.V.I, and a group with the highly characteristic symptom of A.A.D. Following active movement a fall of 80",, in the venous pressure at the back of the calf was measured in normal volunteers, while in C.V.I, and A.A.D. patients this fall was diminished to 20-40",,. Measurement on the big toe showed an average pressure fall of 60",, as a result of passive action in both normal volunteers and C.V.I, patients, thus demonstrating in the latter a normal foot-pump function notwithstanding an impaired calf muscle pump. In patients with A.A.D. a pressure fall of only 30",, was measured on the big toe in response to passive action. Thus the patients with A.A.D. have not only an insufficiency of the calf muscle pump but also an obvious impairment of the venous foot-pump. REFERENCES MALI, J . W . H . & KUIPER J.P. (1965) Acroangiodermatitis of the foot. Archives of Dermatology, 92, 515. KtiiPER, J.P. (1966) Venous pressure determination. Dermatologica, 132, 206, KUIPER, L.P. & VAN DE STAAK, W.J.B.M. (1970) Experiences with the combined use of three methods for measuring peripheral circulation. Current Problems in Dermatology, 3, 164,
Course of nickel contact dermatitis P.L.WuBS Department of Dermatology, University of Nijmegen
In April 1978 we tried to review all patients who had visited our out-patient department 5-15 years ago, who showed a clear positive patch test reaction to nickel sulphate, and who lived in the town of Nijmegen. Only twenty out of a total of seventy-three patients could be interrogated; six of them had shown a weak but deflnite patch test reaction (Ni 2 +) and the other fourteen patients had shown a strong reaction to nickel (at least 3-f). The results are presented in Table i. TABLE I. Activity of the dermatitis of nickel contact hypersensitive patients 5-15 years after their first visit to the out-patient department Activity of the dermatitis
Total no, of patients 6(4) 14(7)
patch test reaction Ni 2 + Ni 3 + , 4 + , 5 +
Uninterrupted contact with nickel present
Uninterrupted contact with nickel not present
No eczema Eczema (No, of patients)
No eczema Eczema (No. of patients)
0 0
6 14
6 14
Accidental contact with nickel materials No eczema Eczema (No. of patients)
0 0
In parentheses, number of patients who first visited 5-10 years ago.
6 14
0 0
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This shows that the hypersensitivity to nickel contact has never disappeared though accidental ephemeral contact with nickel (e.g. coins, door handles) is no longer harmful. The influence of the age of the patients and the penetrability of their skin were not found of importance. Whatever the explanation of the diminishing activity of the nickel contact hypersensitivity may be, it can be concluded that our nickel hypersensitive patients no longer experience real harm from their hypersensitivity after it has lasted 5 years. The reliability of the analyses of Co, Cr and Ni in biological liquids D. SPRUIT
Department of Dermatology, University of Nijmegen
Fifteen years ago levels of Co, Cr and Ni were found in blood plasma, scrum and urine which were IOOO times higher than today. At the moment values of about i figjl are usually found, though even ten times lower values (01 //g/l) have recently been reported (Versieck et al., 1978). Newer methods of investigation have increased the sensitivity of the determinations and lowered the threshold of concentrations which can be determined. However, these changes have not been the same for every method and for each element. Neutron activation analysis seems the most promising method for the elements Co and Cr, while for Ni atomic absorption may be preferable. As this method is very sensitive—a concentration of i figll is equivalent to one part of the element per thousand million parts of other molecules—contamination and chemical reactions arise very easily during sampling and handling of the samples. Thus we found in tears 1-2 /;gNi;l after careful sampling while others have found ten times as much. These very small concentrations of elements in the body may be very important when it is considered that at a concentration of 01 ;/g,'l about lOOO molecules of nickel are present in one erythrocyte. The concentration of nickel in the human body is really very low compared with concentrations outside, being, for example, at least 1000 times greater in scalp hair (Spruit & Bongaarts, 1977)^ in house dust (Creason et al, 1975) and in foodstuffs (Ellin, van den Bosch-Tibbesma & Douma, 1978). Even the rainwater caught in the National Park Hoge Veluwe, near the van Gogh Museum, contained five times more nickel than human plasma or urine (Brinkman & Hrubec, 1976). It thus appears that the human body, sensitized or not, is able to keep nickel outside it. REFERENCES BRINKMAN, F.J.J. & HRUBEC, J. (1976) The soil as filter for water infiltration. In: Proceedings van het nationaal symposium over Milieu Hygiine, p. 32. Wageningen, Centrum voor Landbouwpublicaties en Landbouwdocumcntatie. CREASON, J.P., HINNERS, T.A., NUMGARTER, J.E. & PINKERTON, C . (1975) Trace elements in hair, as related to
exposure in metropolitan New York. Clinical Chemistry, 21, 603. ELLEN, G., VAN DEN BOSCH-TIBBESMA, G . & DOUMA, F.F. (1978) Nickel content of various Dutch foodstuffs. Zeitschrift fur Lcbensmittel Untersuchung und Forschung, 166, 145. SPRUIT, D . & BONGAARTS, P.J.M. (1977) Nickel content of plasma, urine and hair in contact dermatitis. Dermatologica, 154.291. VERSIECK, J., HOSTE, J., BARBIER, F . , STEYAERT, H . , DE RIDDER, J. & MICHELS, H . (1978) Determmation of
chromium and cobalt in human serum by neutron activation analysis. Clinical Chemistry, 24, 303. Delayed irritation—an uncommon reaction to hexanediol diacrylate and butanediol diacrylate K . E . M A L T E N AND J . A . C . J . D E N AREND
Department af Dermatology, University of Nijmegen
Ephemeral topical contact with hcxanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years observation of twenty workers utilizing these substances in the
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electron beam coating department of a door factory, contact sensitization did not occur. Clinical characteristics of this delayed irritant contact dermatitis are: (1) It appeared shortly after starting work. The time lag was too short for a contact sensitization (unless the causative agent had a sensitizing capacity of the magnitude of DNCB). (2) Up to 30",. of the workers developed skin lesions. This is the number of patients to be expected with strong sensitizers; however allergic patch test reactions did not occur. (3) The dermatitis showed no tendency to spread beyond areas commonly exposed. (4) The severity of the dermatitis was more dose dependent than expected in a contact allergy. Bullae appeared on the most exposed parts; adjacent sites looked healthy. Sites of maximal exposure were, for instance, the distal nail folds, under rings and watch straps, and other sites accidentally splashed but commonly not washed during working hours, e.g. elbow folds, sides of neek, lower leg (through clothing contamination). (5) Sometimes a so-called dropping-off effect, such as is seen in Berloque dermatitis, was observed (phototoxicity was not likely). (6) In severe cases aching prevailed over itching, especially during the first hours of contact. (7) Discontinuing work contact resulted in straightforward healing without the caprices often seen in allergic contact dermatitis. (8) The patients resumed work in the same department without much trouble after the initial technical difficulties had been overcome and simple preventive advice had been given. In case of contamination immediate removal by first blotting off with a disposable paper cloth, and subsequently blotting off twice with a fresh paper cloth moistened with methyl-ethyl-ketone, appeared most important. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis. Intranuclear particles in kerato-acanthoma: possible association with malignant degeneration W.J.B.M.VAN DE STAAK AND A.J.G.BERGERS
Department of Dermatology, University of Nijmegen
Electron microscopic investigation of ten patients with kerato-acanthoma is reported. Intranuclear virus-like particles, as described by Zelickson & Lynch (1961), were seen in three cases; two of these subsequently underwent malignant degeneration. These findings suggest that it is particularly important to exclude the possibility of malignant change in these tumours when intranuclear particles are found. Both the size of the particles which we observed (400-800 fim) and their paucity make it unlikely that they are viruses and our observations and some reports in the literature indicate that the particles are by no means specific for kerato-aeanthoma.
REFERENCE
ZELICKSON, A.S. & LYNCH, F.W. (1961) Electron-microscopy of virus-like particles in a kerato-acanthoma. Journal of Investigative Dermatology, 37, 79.
Clinical application of flow cytometry N.CROMBAG AND F.BAUER
Department of Dermatology, University of Nijmegen
Improvement in chemotherapy for psoriasis depends on a better understanding, both of the kinetics of the psoriatic plaque and of the specific mechanisms of drug action.
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We studied the changes in DNA distribution in psoriatic lesions during therapy with flow cytometry, which enables us to measure the cell cycle parameters of keratinocytes within 1 h (Bauer & de Grood, 1975^ 1976; Bauer, Boezeman & de Grood, 1978). It appeared that dithranol acts by inhibiting the progression of cells through the S phase. Rontgen irradiation (55 Kv 10 mA, 05 mmAl 30 cm, 100 R at the surface of the skin) caused a block in the G2 phase and a reduction of the percentage of cells in the S phase. The main effect of PUVA was a very effective block in G2. The therapeutic effect of the drugs under study is apparently due to the elimination of a specific fraction of the cells from the population. REFERENCES BAUER, F . W . & DE GROOD, R.M. (1975) Impulse cytophotometry in psoriasis. British Journal of Dermatology, 93, 225. BAtJER, F.W. & DE GROOD, R.M. (1976) Improved technique for epidermal celt cycle analysis. British Journal of Dermatology, 95, 565. BAUER, F.W., BOEZEMAN, J. & DE GROOD, R.M. (1978) Cell cycleanalysis in normal and pathological skin. In: Cytophorometry. III, p. 533. European Press, Ghent. T h e p l a s m a m e m b r a n e in psoriasis P.D.MlER, p.VAN DEN KERKHOF, H.ROELFZEMA AND J.GOMMANS
Department of Dermatology, University of Nijmegen
The Biochemistry Unit of the Department of Dermatology in Nijmegen is studying certain aspects of the plasma membrane of keratinocytes. It is postulated that an abnormality in the metabolism of glycoproteins may be responsible for changes which have been reported in the behaviour of hormone receptors, immunoreceptors and membrane transport systems in psoriatic epithelium. Dr J.Gommans described the method of preparing isolated keratinocytes and showed SEM photographs of typical cells derived from normal and psoriatic epidermis. He also described the measurement of the lectin-binding ability of these cells, and concluded that the external architectiu-e of the membrane is significantly modified in the psoriatic lesion. Dr P.D.Mier summarized the results of micro-assays for specific membrane-bound sugars. In general the levels of each sugar were approximately doubled in the psoriatic membrane. This increase may be related to the larger surface area of the psoriatic keratinocyte. Dr P.van de Kerkhof described his investigations of the adenyl cyclase system in isolated keratinocytes. The response of the psoriatic cell to adrenaline is markedly reduced, whereas the response to histamine is unchanged. Perhaps the most interesting finding was that the 'resting' level of cyclic AMP in the psoriatic keratinocyte is significantly low. Dr H.Roelfzema presented preliminary measurements of the rate of synthesis of membrane glycoproteins. The 'pattern' of incorporation of a range of different sugars is quite atypical in the psoriatic cell; this confirms the conclusion from lectin-binding experiments that the architecture of the external cell surface is abnormal in psoriasis. CASE REPORTS Department of Dermatology, University of Nijmegen
(i) Hyperkeratosis excentrica (Resphigi) with localized Bowenoid degeneration N.CROMBAG
J.K., male, aged 52 years. History. Since childhood this patient has had a skin lesion, with a verrucous border, on the medial
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side of the left upper leg. A smaller lesion on the left lower leg has disappeared after Rontgen irradiation 30 years agOj leaving an irregular slightly atrophic area. There are no subjective symptoms. Examination. An irregular, sharply bordered polycyclic eruption is seen extending over almost the whole length of the left upper leg (Fig. i). The border of this lesion consists of keratotic papules, with central atrophy and in places erythema and scaling. On the side of the left big toe and forefoot is a linear hyperkeratotic eruption. Lenticular erythematous lesions with a circinate border of small erythematous papules with a diameter of 3-4 mm are seen on the neck and on the right cheek. The patient also has psoriasis. Investigations. Histology of a biopsy from the border of the lesion on the upper leg shows moderate hyperkeratosis with local parakeratotic areas (Fig. 2). There is mild acanthosis. The dermis shows a uniform perivascular infiltrate.
FIGURE 1. Lesions on the upper leg and knee with psoriasis.
2. Histology of border region on upper leg.
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The lesion on the neck showed hyperkeratosis with focally dyskeratotic cells; the epidermal cells are arranged chaotically with much nuclear and cellular atypia. A slight infiltrate is present fn the dermis. (2) Porokeratosis of Mibelli N.CROMBAG
F.J., male, aged 27 years. History. Since early childhood this patient has had annular verrucous lesions on the back of the left hand, the left elbow, the bridge of the nose and the chin. There have been no subjective complaints and the patient has been in good health otherwise. Previously an excision has been attctnptcd on the back of the hand. There is no family history of this disease.
FIGURE 3 . Porokeratosis of MibcUi. Lesiion on Lli: hand.
Examination. There is an annular, polycyclic blue-red eruption with raised hyperkeratotic edges on the areas described above (Fig. 3). The skin in the centre of the annular area is normal (Fig- 4)Treatment. None. Investigations. Histology shows elongated rete ridges with a central depression filled with keratin, and extensive orthokeratotic hyperkeratosis with local parakeratotic areas under the 'cornoid lamella'; the stratum granulosum is absent. In the dermis a slight mononuclear infiltrate is seen. (3) Degos* disease N.CROMBAG
M.v.K.j female, aged 52 years. History. Since 1976, small, yellow red papules have appeared on the arms, legs and trunk. Later on
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FIGURE 4. Porokeratosis ol MibcUi. Annular lesion on nose.
the papules developed an adherent crust after whose shedding a scar remains. There are no subjective complaints. The patient has otherwise been in good health. Examination. About twenty atrophic, slightly depressed lesions, varying in diameter between 2 and ro mm, are distributed over the arms, legs (Fig. 5) and trunk (Fig. 6). Each lesion is surrounded by a red halo. General exatnination is normal. Investigations. Histology shows a flattened epidermis over a band-like oedema. In the dermis an
FiGURU 5. Degos' disease. Lesions on leg.
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nil i i i m i i i II 19 ' 2 0 FIGURE 6. Single lesion on trunk.
infiammatory infiltrate surrounding the vessels and other adnexae is seen, consisting of lymphocytes and histiocytes. A single blood vessel, high in the dermis, was seen obliterated by a thrombus. Comment. She has had no therapy. New lesions are still appearing. She has till now had no gastrointestinal or neurological symptoms. (4) Degos' disease N.CROMBAG
W.S., male, aged 2 years. History. The patient was born with an eruption on the left sole, left abdominal wall, second toe of the left foot and on the scrotum. Later a number of pinhead sized red papules appeared, in the centre of which a whitish crust developed. Every time the crust falls off a defect remains, which often heals spontaneously, leaving a porcelain-like scar. Examination. Scattered on the trunk, extremities and face there are many white atrophic areas from pitihead to a size of 3-4 mm, surrounded by a red halo. Extensive internal examination revealed no abnormalities. Treatment. For one year he has been treated with ethyloestrenol (Orabolin) 2 mg daily by mouth and phenformin I2'5 mg twice daily by mouth, with laboratory control of the lactate levels, gas analysis and bone age. Comment. In spite of therapy new lesions have developed. So far there have been no signs of gastrointestinal or cerebral complications.
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(5) Chronic localized pemphigoid N.CROMBAG
D.K., female, aged 29 years. History. For 8 years a recurrent lesion has been present on the forehead and sometimes on the temples consisting of red macules with bullae. The lesions appear spontaneously without any apparent reason. They heal to leave an atrophic area. Six months ago we saw a 6 x 4 cm large crythematous lesion on the forehead with central atrophy, papules, crusts and one intact bulla on the border (Fig. 7). There were no other abnormalities on skin or mucosae. General examination revealed no abnormalities.
FIGURE 7. Local pemphigoid. Lesion on lorchcad.
Treatment. Topical corticosteroids. hwestigation. Skin biopsy shows a subcpidermal bulla, focal deposits of fibrin and eosinophils in the dermis. Immunofluorescence shows a heavy deposit of IgG and a slight deposit of C3 at the epidermaldermal border, with none around vessels and adnexae. (6) Lymphangioma circumscriptum L.M.TOTH A.V.L., female, aged 9 years. History. In March 1975, after a short period of malaise and fever, small bullae appeared on the right half of the tongue, which was already swollen. There have been periods of increased swelling and formation of small pustules on the surface, possibly due to secondary infection. Examination. The right half of the tongue is thickened irregularly. Both above and below it is covered with pinhead sized, crythematous papules and livid coloured vesicles, filled with haemorrhagic fluid (Fig. 8). Investigation. Histology shows papillomatosis, and ectatic dilated lymph vessels in the dermis.
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FIGURE 8. Tongue during period of secoiiiiaiy infection.
(7) Pachydermoperiostosis (Touraine-Solente-Gole Syndrome) D.GROENEWEG
J.L., male, aged 26 years. History. At the age of 12 years our patient became aware of the thickening of the skin on his hands and feet. From puberty onwards he developed increased skin thickening in his flexuies and accentuation of the creases on his face and scalp. In 1972 and 1974 he was operated on for ptosis of his eyelids. The elder brother of our patient has the same symptoms, as did their maternal grandfather. Examination. {1) Thickening of the skin on hands, feet (Fig. 9), face and eyelids with spade-shaped enlargement of the fore-arms and legs. (2) Accentuation of the creases on his forehead. (3) Clubbing of the fingers and toes. (4) Hyperhidrosis of the palms and soles. (5) Seborrhoea. (6) Cutis verticis gyrata. (7) Hyperkeratotic linear lines on the palms resembling the so-called 'sandlines of the windblown desert' (Fig. 10). Investigation. Histology shows hyperkeratosis, acanthosis and non-specific lymphocytic infiltration of the cutis. X-rays show widening of fibula and tibia, short phalanges and soft tissue swelling.
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FIGURE 9. Pachydermoperiostosis. Soles.
FIGURE 10. Pachydermoperiostosis. Palms.
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(8) and (9) Siemens' Syndrome I (Keratosis follicularis spinulosa decalvans) H.J.Knops J.K.A., female, aged 18 years (daughter). M.K.A., female, aged 43 years (mother). History. The mother has had a progressive alopecia since her third year, the daughter since he seventh. The eyebrows changed before their sixteenth year in both cases. They have always had a rough and dry skin. No other members of the family have been affected. Examination. The scalps of both show an appearance like the pseudopelade of Brocq, except that the remaining hair follicles have a protruding horny scale. There is lateral loss of hair on the eyebrows and small scars as seen in ulerythema ophryogenes. On the body and extremities there are follicular papules with hyperkeratotic scales; on the extensor surfaces ichthyosis vulgaris. Investigation. Biopsy shows orthokeratosis, flattened epidermis with follicular plugging and widened hairless follicles. Comment. In the fully developed form this syndrome is described only in males. Females develop an incomplete syndrome.
Society Pvoceedin^s
Proceedings of the 213th Meeting of the Netherlands' Society of Dermatologists^ Nijmegen, 27 May 1978 PRESIDENT: DR M.J.WOERDEMAN HOST: PROF. DR J.W.H.MALI SUMMARIES OF PAPERS Treatment of psoriasis with ultraviolet-B light J.BOER, A.A.SCHOTHORST AND D.SUUBMOND
Department of Dermatology, University Hospital, Leiden, The Netherlands The efFect of ultraviolet-B light was investigated in fifteen patients with long-standing, widespread, and stable psoriasis. Patients whose skin lesions had invariably shown considerable improvement (at least 90",,) after consistent exposure to sunlight, usually in combination with seabathing, were selected for this treatment. Irradiation was provided by twelve 122 cm Philips TL 12 40 W fluorescent tubes and twelve 61 cm 20 W tubes mounted on two hinged upright frames. These lamps emit a continuous wavelength spectrum ranging from approximately 280 to 380 nm with a peak at 305 nm. At a height of 80 cm from the floor, the irradiance was 3-1 mW/cm'at a distance of 50 cm from the panel and i-5mW/cm-at 100 cm. Betore treatment was started, light tests were carried out with the light panel to determine the MED on the back and a lower leg for the wavelength spectrum from 280 to 380 nm. The first therapeutic light dose administered was equal to the sub-MED. In almost all of the patients the sub-MED was found to be definitely lower for the back than for the legs. Consequently, in most cases additional irradiation was given to the lower legs and the elbows during the treatment. The dosages were gradually increased by 20-40",, per session, depending on the increasing skin tolerance. During the initial phase (clearing phase) four irradiations a week were given. An effort was made to keep the longest exposure time for each side of the body below 30 min during the initial phase and below 10 min during the maintenance phase. Thirteen of the fifteen patients showed an improvement amounting to between 80 and 100",, relative to the pretreatment condition. The initial phase required an average of twenty-three irradiations. In the maintenance phase, twelve of the fifteen patients showed an improvement of So-ioo','« on a schedule of one irradiation every 1-5 weeks. The high therapeutic scores may, in our opinion, be attributed to one or more of three factors: the selection of patients, the type of light source, and the method of irradiation. Acrodermatitis and the foot-pump function J.P.KuiPER,
A.J.M.BRAKKEE AND J.J.COLLARD
Department of Dermatology, University of Nijmegen In t965, Mali & Kuiper described the syndrome of acroangiodcrmatits (A.A.D.), so-called pseudoKaposi, considering it as a peculiar manifestation of chronic venous insufficiency (C.V.I.) and suggesting 0OO7-O963/79/05oo-0599$O2.oo Ci t979 British Association of Dermatologists 599
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that in these patients in addition to incompetence of the calf muscle piunp the venous foot-pump action is particularly impaired. Kuiper (1966) gave some quantitative information about this foot-pump activity. Using a non-invasive method of venous pressure determination (Kuiper & van de Staak, 1970) quantitative data can more easily be obtained. The venous pressure fail was measured following active movement of foot and leg and following passive movement by kneading the foot with both hands. The measurements were performed at three different levels—the big toe, the middle of the foot and just above the ankle region—in a group of normal volunteers, a group of patients suffering from C.V.I, and a group with the highly characteristic symptom of A.A.D. Following active movement a fall of 80",, in the venous pressure at the back of the calf was measured in normal volunteers, while in C.V.I, and A.A.D. patients this fall was diminished to 20-40",,. Measurement on the big toe showed an average pressure fall of 60",, as a result of passive action in both normal volunteers and C.V.I, patients, thus demonstrating in the latter a normal foot-pump function notwithstanding an impaired calf muscle pump. In patients with A.A.D. a pressure fall of only 30",, was measured on the big toe in response to passive action. Thus the patients with A.A.D. have not only an insufficiency of the calf muscle pump but also an obvious impairment of the venous foot-pump. REFERENCES MALI, J . W . H . & KUIPER J.P. (1965) Acroangiodermatitis of the foot. Archives of Dermatology, 92, 515. KtiiPER, J.P. (1966) Venous pressure determination. Dermatologica, 132, 206, KUIPER, L.P. & VAN DE STAAK, W.J.B.M. (1970) Experiences with the combined use of three methods for measuring peripheral circulation. Current Problems in Dermatology, 3, 164,
Course of nickel contact dermatitis P.L.WuBS Department of Dermatology, University of Nijmegen
In April 1978 we tried to review all patients who had visited our out-patient department 5-15 years ago, who showed a clear positive patch test reaction to nickel sulphate, and who lived in the town of Nijmegen. Only twenty out of a total of seventy-three patients could be interrogated; six of them had shown a weak but deflnite patch test reaction (Ni 2 +) and the other fourteen patients had shown a strong reaction to nickel (at least 3-f). The results are presented in Table i. TABLE I. Activity of the dermatitis of nickel contact hypersensitive patients 5-15 years after their first visit to the out-patient department Activity of the dermatitis
Total no, of patients 6(4) 14(7)
patch test reaction Ni 2 + Ni 3 + , 4 + , 5 +
Uninterrupted contact with nickel present
Uninterrupted contact with nickel not present
No eczema Eczema (No, of patients)
No eczema Eczema (No. of patients)
0 0
6 14
6 14
Accidental contact with nickel materials No eczema Eczema (No. of patients)
0 0
In parentheses, number of patients who first visited 5-10 years ago.
6 14
0 0
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This shows that the hypersensitivity to nickel contact has never disappeared though accidental ephemeral contact with nickel (e.g. coins, door handles) is no longer harmful. The influence of the age of the patients and the penetrability of their skin were not found of importance. Whatever the explanation of the diminishing activity of the nickel contact hypersensitivity may be, it can be concluded that our nickel hypersensitive patients no longer experience real harm from their hypersensitivity after it has lasted 5 years. The reliability of the analyses of Co, Cr and Ni in biological liquids D. SPRUIT
Department of Dermatology, University of Nijmegen
Fifteen years ago levels of Co, Cr and Ni were found in blood plasma, scrum and urine which were IOOO times higher than today. At the moment values of about i figjl are usually found, though even ten times lower values (01 //g/l) have recently been reported (Versieck et al., 1978). Newer methods of investigation have increased the sensitivity of the determinations and lowered the threshold of concentrations which can be determined. However, these changes have not been the same for every method and for each element. Neutron activation analysis seems the most promising method for the elements Co and Cr, while for Ni atomic absorption may be preferable. As this method is very sensitive—a concentration of i figll is equivalent to one part of the element per thousand million parts of other molecules—contamination and chemical reactions arise very easily during sampling and handling of the samples. Thus we found in tears 1-2 /;gNi;l after careful sampling while others have found ten times as much. These very small concentrations of elements in the body may be very important when it is considered that at a concentration of 01 ;/g,'l about lOOO molecules of nickel are present in one erythrocyte. The concentration of nickel in the human body is really very low compared with concentrations outside, being, for example, at least 1000 times greater in scalp hair (Spruit & Bongaarts, 1977)^ in house dust (Creason et al, 1975) and in foodstuffs (Ellin, van den Bosch-Tibbesma & Douma, 1978). Even the rainwater caught in the National Park Hoge Veluwe, near the van Gogh Museum, contained five times more nickel than human plasma or urine (Brinkman & Hrubec, 1976). It thus appears that the human body, sensitized or not, is able to keep nickel outside it. REFERENCES BRINKMAN, F.J.J. & HRUBEC, J. (1976) The soil as filter for water infiltration. In: Proceedings van het nationaal symposium over Milieu Hygiine, p. 32. Wageningen, Centrum voor Landbouwpublicaties en Landbouwdocumcntatie. CREASON, J.P., HINNERS, T.A., NUMGARTER, J.E. & PINKERTON, C . (1975) Trace elements in hair, as related to
exposure in metropolitan New York. Clinical Chemistry, 21, 603. ELLEN, G., VAN DEN BOSCH-TIBBESMA, G . & DOUMA, F.F. (1978) Nickel content of various Dutch foodstuffs. Zeitschrift fur Lcbensmittel Untersuchung und Forschung, 166, 145. SPRUIT, D . & BONGAARTS, P.J.M. (1977) Nickel content of plasma, urine and hair in contact dermatitis. Dermatologica, 154.291. VERSIECK, J., HOSTE, J., BARBIER, F . , STEYAERT, H . , DE RIDDER, J. & MICHELS, H . (1978) Determmation of
chromium and cobalt in human serum by neutron activation analysis. Clinical Chemistry, 24, 303. Delayed irritation—an uncommon reaction to hexanediol diacrylate and butanediol diacrylate K . E . M A L T E N AND J . A . C . J . D E N AREND
Department af Dermatology, University of Nijmegen
Ephemeral topical contact with hcxanediol diacrylate and butanediol diacrylate may cause delayed irritant dermatitis. During 4 years observation of twenty workers utilizing these substances in the
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electron beam coating department of a door factory, contact sensitization did not occur. Clinical characteristics of this delayed irritant contact dermatitis are: (1) It appeared shortly after starting work. The time lag was too short for a contact sensitization (unless the causative agent had a sensitizing capacity of the magnitude of DNCB). (2) Up to 30",. of the workers developed skin lesions. This is the number of patients to be expected with strong sensitizers; however allergic patch test reactions did not occur. (3) The dermatitis showed no tendency to spread beyond areas commonly exposed. (4) The severity of the dermatitis was more dose dependent than expected in a contact allergy. Bullae appeared on the most exposed parts; adjacent sites looked healthy. Sites of maximal exposure were, for instance, the distal nail folds, under rings and watch straps, and other sites accidentally splashed but commonly not washed during working hours, e.g. elbow folds, sides of neek, lower leg (through clothing contamination). (5) Sometimes a so-called dropping-off effect, such as is seen in Berloque dermatitis, was observed (phototoxicity was not likely). (6) In severe cases aching prevailed over itching, especially during the first hours of contact. (7) Discontinuing work contact resulted in straightforward healing without the caprices often seen in allergic contact dermatitis. (8) The patients resumed work in the same department without much trouble after the initial technical difficulties had been overcome and simple preventive advice had been given. In case of contamination immediate removal by first blotting off with a disposable paper cloth, and subsequently blotting off twice with a fresh paper cloth moistened with methyl-ethyl-ketone, appeared most important. The disease must be distinguished from allergic contact dermatitis, acute irritant dermatitis and cumulative irritant dermatitis. Intranuclear particles in kerato-acanthoma: possible association with malignant degeneration W.J.B.M.VAN DE STAAK AND A.J.G.BERGERS
Department of Dermatology, University of Nijmegen
Electron microscopic investigation of ten patients with kerato-acanthoma is reported. Intranuclear virus-like particles, as described by Zelickson & Lynch (1961), were seen in three cases; two of these subsequently underwent malignant degeneration. These findings suggest that it is particularly important to exclude the possibility of malignant change in these tumours when intranuclear particles are found. Both the size of the particles which we observed (400-800 fim) and their paucity make it unlikely that they are viruses and our observations and some reports in the literature indicate that the particles are by no means specific for kerato-aeanthoma.
REFERENCE
ZELICKSON, A.S. & LYNCH, F.W. (1961) Electron-microscopy of virus-like particles in a kerato-acanthoma. Journal of Investigative Dermatology, 37, 79.
Clinical application of flow cytometry N.CROMBAG AND F.BAUER
Department of Dermatology, University of Nijmegen
Improvement in chemotherapy for psoriasis depends on a better understanding, both of the kinetics of the psoriatic plaque and of the specific mechanisms of drug action.
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We studied the changes in DNA distribution in psoriatic lesions during therapy with flow cytometry, which enables us to measure the cell cycle parameters of keratinocytes within 1 h (Bauer & de Grood, 1975^ 1976; Bauer, Boezeman & de Grood, 1978). It appeared that dithranol acts by inhibiting the progression of cells through the S phase. Rontgen irradiation (55 Kv 10 mA, 05 mmAl 30 cm, 100 R at the surface of the skin) caused a block in the G2 phase and a reduction of the percentage of cells in the S phase. The main effect of PUVA was a very effective block in G2. The therapeutic effect of the drugs under study is apparently due to the elimination of a specific fraction of the cells from the population. REFERENCES BAUER, F . W . & DE GROOD, R.M. (1975) Impulse cytophotometry in psoriasis. British Journal of Dermatology, 93, 225. BAtJER, F.W. & DE GROOD, R.M. (1976) Improved technique for epidermal celt cycle analysis. British Journal of Dermatology, 95, 565. BAUER, F.W., BOEZEMAN, J. & DE GROOD, R.M. (1978) Cell cycleanalysis in normal and pathological skin. In: Cytophorometry. III, p. 533. European Press, Ghent. T h e p l a s m a m e m b r a n e in psoriasis P.D.MlER, p.VAN DEN KERKHOF, H.ROELFZEMA AND J.GOMMANS
Department of Dermatology, University of Nijmegen
The Biochemistry Unit of the Department of Dermatology in Nijmegen is studying certain aspects of the plasma membrane of keratinocytes. It is postulated that an abnormality in the metabolism of glycoproteins may be responsible for changes which have been reported in the behaviour of hormone receptors, immunoreceptors and membrane transport systems in psoriatic epithelium. Dr J.Gommans described the method of preparing isolated keratinocytes and showed SEM photographs of typical cells derived from normal and psoriatic epidermis. He also described the measurement of the lectin-binding ability of these cells, and concluded that the external architectiu-e of the membrane is significantly modified in the psoriatic lesion. Dr P.D.Mier summarized the results of micro-assays for specific membrane-bound sugars. In general the levels of each sugar were approximately doubled in the psoriatic membrane. This increase may be related to the larger surface area of the psoriatic keratinocyte. Dr P.van de Kerkhof described his investigations of the adenyl cyclase system in isolated keratinocytes. The response of the psoriatic cell to adrenaline is markedly reduced, whereas the response to histamine is unchanged. Perhaps the most interesting finding was that the 'resting' level of cyclic AMP in the psoriatic keratinocyte is significantly low. Dr H.Roelfzema presented preliminary measurements of the rate of synthesis of membrane glycoproteins. The 'pattern' of incorporation of a range of different sugars is quite atypical in the psoriatic cell; this confirms the conclusion from lectin-binding experiments that the architecture of the external cell surface is abnormal in psoriasis. CASE REPORTS Department of Dermatology, University of Nijmegen
(i) Hyperkeratosis excentrica (Resphigi) with localized Bowenoid degeneration N.CROMBAG
J.K., male, aged 52 years. History. Since childhood this patient has had a skin lesion, with a verrucous border, on the medial
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side of the left upper leg. A smaller lesion on the left lower leg has disappeared after Rontgen irradiation 30 years agOj leaving an irregular slightly atrophic area. There are no subjective symptoms. Examination. An irregular, sharply bordered polycyclic eruption is seen extending over almost the whole length of the left upper leg (Fig. i). The border of this lesion consists of keratotic papules, with central atrophy and in places erythema and scaling. On the side of the left big toe and forefoot is a linear hyperkeratotic eruption. Lenticular erythematous lesions with a circinate border of small erythematous papules with a diameter of 3-4 mm are seen on the neck and on the right cheek. The patient also has psoriasis. Investigations. Histology of a biopsy from the border of the lesion on the upper leg shows moderate hyperkeratosis with local parakeratotic areas (Fig. 2). There is mild acanthosis. The dermis shows a uniform perivascular infiltrate.
FIGURE 1. Lesions on the upper leg and knee with psoriasis.
2. Histology of border region on upper leg.
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The lesion on the neck showed hyperkeratosis with focally dyskeratotic cells; the epidermal cells are arranged chaotically with much nuclear and cellular atypia. A slight infiltrate is present fn the dermis. (2) Porokeratosis of Mibelli N.CROMBAG
F.J., male, aged 27 years. History. Since early childhood this patient has had annular verrucous lesions on the back of the left hand, the left elbow, the bridge of the nose and the chin. There have been no subjective complaints and the patient has been in good health otherwise. Previously an excision has been attctnptcd on the back of the hand. There is no family history of this disease.
FIGURE 3 . Porokeratosis of MibcUi. Lesiion on Lli: hand.
Examination. There is an annular, polycyclic blue-red eruption with raised hyperkeratotic edges on the areas described above (Fig. 3). The skin in the centre of the annular area is normal (Fig- 4)Treatment. None. Investigations. Histology shows elongated rete ridges with a central depression filled with keratin, and extensive orthokeratotic hyperkeratosis with local parakeratotic areas under the 'cornoid lamella'; the stratum granulosum is absent. In the dermis a slight mononuclear infiltrate is seen. (3) Degos* disease N.CROMBAG
M.v.K.j female, aged 52 years. History. Since 1976, small, yellow red papules have appeared on the arms, legs and trunk. Later on
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FIGURE 4. Porokeratosis ol MibcUi. Annular lesion on nose.
the papules developed an adherent crust after whose shedding a scar remains. There are no subjective complaints. The patient has otherwise been in good health. Examination. About twenty atrophic, slightly depressed lesions, varying in diameter between 2 and ro mm, are distributed over the arms, legs (Fig. 5) and trunk (Fig. 6). Each lesion is surrounded by a red halo. General exatnination is normal. Investigations. Histology shows a flattened epidermis over a band-like oedema. In the dermis an
FiGURU 5. Degos' disease. Lesions on leg.
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nil i i i m i i i II 19 ' 2 0 FIGURE 6. Single lesion on trunk.
infiammatory infiltrate surrounding the vessels and other adnexae is seen, consisting of lymphocytes and histiocytes. A single blood vessel, high in the dermis, was seen obliterated by a thrombus. Comment. She has had no therapy. New lesions are still appearing. She has till now had no gastrointestinal or neurological symptoms. (4) Degos' disease N.CROMBAG
W.S., male, aged 2 years. History. The patient was born with an eruption on the left sole, left abdominal wall, second toe of the left foot and on the scrotum. Later a number of pinhead sized red papules appeared, in the centre of which a whitish crust developed. Every time the crust falls off a defect remains, which often heals spontaneously, leaving a porcelain-like scar. Examination. Scattered on the trunk, extremities and face there are many white atrophic areas from pitihead to a size of 3-4 mm, surrounded by a red halo. Extensive internal examination revealed no abnormalities. Treatment. For one year he has been treated with ethyloestrenol (Orabolin) 2 mg daily by mouth and phenformin I2'5 mg twice daily by mouth, with laboratory control of the lactate levels, gas analysis and bone age. Comment. In spite of therapy new lesions have developed. So far there have been no signs of gastrointestinal or cerebral complications.
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(5) Chronic localized pemphigoid N.CROMBAG
D.K., female, aged 29 years. History. For 8 years a recurrent lesion has been present on the forehead and sometimes on the temples consisting of red macules with bullae. The lesions appear spontaneously without any apparent reason. They heal to leave an atrophic area. Six months ago we saw a 6 x 4 cm large crythematous lesion on the forehead with central atrophy, papules, crusts and one intact bulla on the border (Fig. 7). There were no other abnormalities on skin or mucosae. General examination revealed no abnormalities.
FIGURE 7. Local pemphigoid. Lesion on lorchcad.
Treatment. Topical corticosteroids. hwestigation. Skin biopsy shows a subcpidermal bulla, focal deposits of fibrin and eosinophils in the dermis. Immunofluorescence shows a heavy deposit of IgG and a slight deposit of C3 at the epidermaldermal border, with none around vessels and adnexae. (6) Lymphangioma circumscriptum L.M.TOTH A.V.L., female, aged 9 years. History. In March 1975, after a short period of malaise and fever, small bullae appeared on the right half of the tongue, which was already swollen. There have been periods of increased swelling and formation of small pustules on the surface, possibly due to secondary infection. Examination. The right half of the tongue is thickened irregularly. Both above and below it is covered with pinhead sized, crythematous papules and livid coloured vesicles, filled with haemorrhagic fluid (Fig. 8). Investigation. Histology shows papillomatosis, and ectatic dilated lymph vessels in the dermis.
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FIGURE 8. Tongue during period of secoiiiiaiy infection.
(7) Pachydermoperiostosis (Touraine-Solente-Gole Syndrome) D.GROENEWEG
J.L., male, aged 26 years. History. At the age of 12 years our patient became aware of the thickening of the skin on his hands and feet. From puberty onwards he developed increased skin thickening in his flexuies and accentuation of the creases on his face and scalp. In 1972 and 1974 he was operated on for ptosis of his eyelids. The elder brother of our patient has the same symptoms, as did their maternal grandfather. Examination. {1) Thickening of the skin on hands, feet (Fig. 9), face and eyelids with spade-shaped enlargement of the fore-arms and legs. (2) Accentuation of the creases on his forehead. (3) Clubbing of the fingers and toes. (4) Hyperhidrosis of the palms and soles. (5) Seborrhoea. (6) Cutis verticis gyrata. (7) Hyperkeratotic linear lines on the palms resembling the so-called 'sandlines of the windblown desert' (Fig. 10). Investigation. Histology shows hyperkeratosis, acanthosis and non-specific lymphocytic infiltration of the cutis. X-rays show widening of fibula and tibia, short phalanges and soft tissue swelling.
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FIGURE 9. Pachydermoperiostosis. Soles.
FIGURE 10. Pachydermoperiostosis. Palms.
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(8) and (9) Siemens' Syndrome I (Keratosis follicularis spinulosa decalvans) H.J.Knops J.K.A., female, aged 18 years (daughter). M.K.A., female, aged 43 years (mother). History. The mother has had a progressive alopecia since her third year, the daughter since he seventh. The eyebrows changed before their sixteenth year in both cases. They have always had a rough and dry skin. No other members of the family have been affected. Examination. The scalps of both show an appearance like the pseudopelade of Brocq, except that the remaining hair follicles have a protruding horny scale. There is lateral loss of hair on the eyebrows and small scars as seen in ulerythema ophryogenes. On the body and extremities there are follicular papules with hyperkeratotic scales; on the extensor surfaces ichthyosis vulgaris. Investigation. Biopsy shows orthokeratosis, flattened epidermis with follicular plugging and widened hairless follicles. Comment. In the fully developed form this syndrome is described only in males. Females develop an incomplete syndrome.
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