The Scandinavian multicenter photopatch study 1980-1985: final report.

At 16 different dermatology clinics in Scandinavia from 1980-1985, photopatch testing was performed on 1993 patients with suspected photodermatosis. The collective results are presented in this article. The most common cause of sun-related dermatosis was polymorphic light eruption (PLE) (38%), while secondary aggravation of pre-existing skin diseases was established in 16% of the patient group. Photocontact dermatitis (11%) and contact dermatitis (10%) were responsible for 274 and 369 positive test reactions (respectively) on photopatch testing using the SPDRG standard series. Musk ambrette and para-aminobenzoic acid were the leading photosensitizers, while perfume mixture, balsam of Peru and lichen mixture were the most frequent causes of contact sensitivity. The principal photoallergens and contact allergens in the PLE, persistent light reaction and actinic reticuloid groups are discussed, together with the problems, risks and possible mechanisms of induction of photosensitization in these patients. The incidence, causes and diagnostic and therapeutic implications of secondary sunscreen sensitivity in these groups are also addressed.

Cutaneous sarcoidosis in Caucasians.

One hundred eighty-eight Caucasian patients with cutaneous sarcoid lesions were studied prospectively. Twenty-five had erythema nodosum, while 163 had infiltrative cutaneous lesions. One hundred thirty-eight patients had systemic as well as cutaneous lesions, and fifty had cutaneous lesions only. All types of clinical lesions were seen among patients with cutaneous lesions only. The extent of cutaneous lesions did not correlate with the extent of systemic disease. Papular lesions were relatively uncommon and occurred as the only manifestation of the disease or were associated with hilar adenopathy and acute disease. Lupus pernio, scar infiltrates, and plaque lesions were the most common clinical lesions and were typically chronic and commonly associated with pulmonary mottling and/or fibrosis. Forty-eight of 127 had a histologically positive Kveim test. Among patients followed for more than 2 years, dinitrochlorobenzene (DNCB) sensitivity was higher among those with acute disease than among those with chronic disease. Seventy-nine patients with infiltrative cutaneous lesions were followed until the cutaneous lesions had healed. Those with lupus pernio were often left with unsightly telangiectatic scars, while the other types of lesions left either pale, slightly depressed scars or no scars at all.

Relative ultraviolet spectral intensity of direct solar radiation, sky radiation and surface reflections. Relative contribution of natural sources to the outdoor UV irradiation of man.

Relative measurements of UVA and UVB radiation from the sun and the sky, as well as the reflected intensity from various land and water surfaces, have been carried out in the Copenhagen area. The measurements were taken in January and in the period April through July and supplemented by measurements in Greenland during May. Likewise, the angular distribution of direct solar radiation and sky radiation close to the direction of the sun was measured with a 0.5 degree field of view. Absolute UV irradiances were measured with detector-filter combinations. Calculations of the relative contributions of direct solar radiation, sky radiation and reflected radiation to the irradiation of a standing person show, in particular, that if seawater with waves is the surrounding scene, its reflected radiation will account for more than 10% of the received UV dose.

Development of polyneuropathy during thalidomide therapy.

Seven patients with prurigo nodularis and one with aphthous stomatitis were given 40-115 g of thalidomide for 1 to 6 years. They all developed a predominantly sensory peripheral neuropathy mainly involving the lower limbs. Five patients had an unpleasant tight feeling around the feet. Nerve conduction studies showed small sensory action potentials from the lower limbs with normal or only mild slowing of sensory conduction velocity indicating an axonal neuropathy. The dermatological disorder improved dramatically in all, but treatment had to be discontinued because of the severe side-effects. Thalidomide, if used, should be given only over a short period because of its neurotoxic effect.

Serum angiotensin-converting enzyme in sarcoidosis and psoriasis.

Untreated pulmonary sarcoidosis is associated with an increased level of serum angiotensin-converting enzyme (SACE), which is regarded as a valuable method of diagnosing sarcoidosis and measuring the activity of the disease. The level of SACE in cutaneous sarcoidosis or other skin diseases has not been clearly established. We therefore examined SACE in 31 patients with systemic sarcoidosis, including cutaneous manifestations, and 12 patients with isolated cutaneous sarcoidosis. Also, 23 patients with psoriasis were studied. The level of SACE was generally elevated only in patients with untreated systemic sarcoidosis, whereas it was normal in cutaneous sarcoidosis and psoriasis. If the level of SACE is elevated in "isolated" cutaneous sarcoidosis, systemic disease must be strongly suspected.

Dermal elastosis in hairless mice after UV-B and UV-A applied simultaneously, separately or sequentially.

The elastosis-inducing capacity of UV-A and UV-B was studied in the skin of hairless mice. After irradiation with UV-B and UV-A applied either simultaneously, separately or sequentially, the degree of elastosis in the dermis was microscopically evaluated. This semi-quantitative method showed no significant elastosis in the UV-A irradiated mice, and moderate elastosis in the UV-B irradiated mice. Heavy elastosis was observed when the mice were exposed sequentially to UV-B and a large dose of UV-A, but if a moderate dose of UV-A was given simultaneously with UV-B, the degree of elastosis was slightly reduced compared with the elastosis induced by UV-B alone.

The Scandinavian multicenter photopatch study. Preliminary results.

The Scandinavian photopatch test procedure has been applied to 745 patients with suspected photodermatoses during the years 1980-1981. Our experience has been encouraging with the recording of several relevant reactions. A total of 132 positive photocontact reactions and 120 ordinary contact reactions were seen. Photocontact reactions to musk ambrette (19 cases) and PABA (19 cases) were surprisingly frequent. The next most common photocontact reactions were to promethazine (24), chlorpromazine (22 cases) and fentichlor (12). Ordinary contact reactions were observed to balsam of Peru (30), PABA (23), lichen mix (21), wood mix (14) and to perfume mix (10).

Entero-hepatic cycling of methotrexate estimated by use of the D-isomer as a reference marker.

The absorption and elimination kinetics of 4-amino-N10-methylpteroyl-D-glutamic acid (D-MTX), the optical isomer of methotrexate (L-MTX), were examined. Test doses of 10 mg D-MTX were administered i.v. and orally to nine patients and its plasma concentration and urinary excretion were followed. The plasma curves after an i.v. bolus injection of D-MTX declined strictly biexponentially and reached zero after about 16 h. The elimination rate constants were estimated as the terminal first order rate constants. The absorption of orally administered D-MTX, estimated by its 24 h urinary recovery, in all cases was less than 3% of the dose administered. The insignificant intestinal absorption made it possible to estimate the renal and biliary secretion rates of D-MTX from the overall elimination rate constant and from the fraction of the dose excreted in urine. In three of the patients, elimination rate constants both for D-MTX and L-MTX were obtained. The renal elimination rates of the two compounds were found to be nearly identical. The median ratio of biliary/renal excretion of D-MTX was 0.94 (range 0.41-1.50), which indicates extensive entero-hepatic cycling and active absorption of L-MTX at the therapeutic dose levels used in psoriasis.

The carcinogenic effect of UVA irradiation.

The carcinogenic effect of UVA radiation (from Philips black light tubes filtered through a 2 mm-thick glass plate to eliminate the radiation below 320 nm) was studied in 7 groups of 25 lightly pigmented hairless mice. Irradiation with a moderate daily dose of combined UVB and UVA for 3 months induced a tumor incidence of 0.22 after 58 weeks. When the combined UVB and UVA irradiation was followed by filtered UVA for 2, 4, or 6 months, the tumor incidence was marginally significantly increased to 0.42, 0.48, and 0.50 (p less than 0.05), respectively. However, irradiation with the moderate dose of combined UVB and UVA induced a slight but not significantly lower tumor incidence as compared to UVB alone (0.22 vs 0.30, p greater than 0.1). UVA alone induced no tumors. It thus appears that in hairless mice initially exposed to a combination of UVB and UVA, subsequent continued irradiation with UVA increases tumor incidence. While only marginally statistically significant, tumor incidence in these animals seems to increase with duration and hence total UVA exposure. Furthermore, it is suggested that the photoaugmentative carcinogenic effect of UVA irradiation from unfiltered UVA bulbs can be reduced by attenuating the shorter wavelengths of the radiation.

Carcinogenic effect of sequential artificial sunlight and UV-A irradiation in hairless mice. Consequences for solarium 'therapy'.

The carcinogenic effect of artificial UV sunlight followed by UV-A irradiation in human solaria doses has been studied with the use of the hairless mouse as an animal model. Artificial sunlight exposure alone induced only a moderate skin tumor incidence (animals with at least one tumor) of 0.15 after one year, and UV-A irradiation alone induced no tumor formation. However, the combination of artificial sunlight exposure and subsequent UV-A irradiation significantly increased the tumor incidence to 0.72. We conclude that, in humans, tanning with UV-A for cosmetic purposes may not be an innocuous procedure.

Solar Simulators: modifications for testing with visible light.

The Berger Solar Simulator is designed to test light-sensitive patients for their sensitivity to ultraviolet light. The present modification was performed to make testing with UV and visible light possible. The modification consists in replacing the dicroic mirror with a beam splitter (BSP 580) and the filters with a WG 340 allowing 340-565 nm to pass. Subdivision of that spectrum is performed by inserting a Wratten 12 (500-565 nm) or a Wratten 2B (400-565 nm). Infrared is excluded by a KG3 filter.

Direct and indirect effects of UVA on skin vessel leakiness.

By using the suction blister technique we have investigated the leakiness of skin vessels in healthy volunteers after whole-body suberythemogenic doses of UVA radiation (a quadrant on one side of the abdominal skin was shielded with lead-rubber). The accumulation of intravenously injected labeled albumin in blister fluid was slightly elevated 1 day after irradiation and increased significantly 2 days later. The blister concentrations of 4 endogenous plasma proteins (albumin, transferrin, IgG, and alpha 2-macroglobulin) were elevated 1 day after radiation exposure and normalized 2 days later. All changes were equal on irradiated and nonirradiated skin. It is concluded that UVA radiation can induce a continued or biphasic increased leakage of plasma proteins in the skin vessels, due to a humoral rather than to a direct physical effect of the radiation on the vessel walls. It is suggested that an increased microvascular leakiness in organs other than the skin might be present.

Sunscreens for delay of ultraviolet induction of skin tumors.

Sunscreens with different sun protection factors (SPFs) have been tested for their capability of delaying or preventing actinic damage and skin cancer development in groups of hairless, pigmented mice exposed to artificial ultraviolet (UV) light of increasing intensity. The dose delivered was less than or equal to 1 minimal erythema dose (MED) in the group of untreated mice, so that the mice to which sunscreens were applied never obtained a sunburn after UV exposure. The quality of UV light was similar to bright midday sun at a latitude of 56 degrees (city of Copenhagen). Tumorigenesis was demonstrated to be delayed corresponding to the SPF claimed by the manufacturer, but almost all of the UV-irradiated mice developed skin tumors. Histologic examination revealed actinic degeneration and tumors of squamous cell type with marked variation in differentiation. Metastases to lymph nodes and lungs were found in only 10%. Toxic reactions, such as eczematous-like skin reactions, dark coloring, and amyloidosis, were observed predominantly in the group treated with the sunscreen of highest SPF value. Long-term investigations seem to be necessary to unveil these problems--in particular, the specific SPF value, in sunscreens, that should be recommended to the public for prevention or delay of actinic damage and/or cancer development.

The Scandinavian standard photopatch test procedure.

Recognizing the growing need for international standardization of photopatch testing techniques, a standard procedure has been used by Scandinavian dermatological clinics since January 1980. The set-up includes a standardized patient examination scheme, including phototest evaluation of the patient's UVA- and UVB-sensitivity, a standard photopatch tray containing 19 substances, and uniform techniques and criteria for the application and evaluation of the tests. Although modifications may be necessary in the future, preliminary experience with the Scandinavian photopatch set-up has been encouraging, and several positive reactions to most of the substances used have been recorded in the first 350 patients tested.

Microvascular leakage of plasma proteins after PUVA and UVA.

The transcapillary escape rate of albumin (TERalb), i.e., the fraction of intravascular albumin mass passing to the extravascular space per unit time, is a parameter of the leakage of macromolecules from the total microvasculature. In patients with psoriasis short-term PUVA treatment induces an increase in TERalb. In this study TERalb was measured in 3 groups of normal humans treated with PUVA, UVA and 8-methoxypsoralen. Treatment with PUVA and UVA caused a statistically significant increase in TERalb, whereas treatment with 8-methoxypsoralen did not induce any measurable changes. It is concluded that the UVA irradiation causes the abnormal leakage of macromolecules, whereas psoralen is not the responsible component. Furthermore the phenomenon can be elicited in normals and is not based on a preexisting psoriasis.