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This study compares the action spectra on two new patients with actinic reticuloid (AR), with one previously reported patient. All three patients had exquisite photosensitivity in the UVB range being up to 27 times more sensitive than controls. Sensitivity also increased into the UVA Range, all up to 335 nm and, one into the visible. Their photosensitivity made evaluation of the Sun Protection Factor (SPF) of selected, more recent, high-numbered sunscreens easier to compare, because of the shorter time of the minimal erythema dose when tested with a solar simulator. A sunscreen containing butyl methoxydibenzoylmethane (Parsol 1789) with an overall SPF of 16 was not as effective at protecting the actinic reticuloid patients as a higher SPF numbered sunscreen containing a benzophenone (SPF of 40). The Parsol 1789 gave a protection value of 5 in the UVA Range, compared to one of 3 given by the sunscreen containing benzophenone. The SPFs of seven of these commerically available high-numbered sunscreens were compared with controls.

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BACKGROUND: The safety of psoralen plus ultraviolet A (PUVA) light therapy has been an issue of debate. A few multiple-center cooperative studies have reported an increase of basal cell and squamous cell carcinomas among PUVA-treated patients. In our institute, more than 1000 patients have been treated with PUVA since 1975. OBJECTIVE: We investigated the incidence of skin cancer among patients who received high doses of PUVA to see whether such incidence increased. METHODS: This is a historical cohort study of two comparison groups of patients. Subjects under study were 492 psoriasis patients who received PUVA treatments between 1975 and 1989. One group of 103 patients, defined as the high-dose group, received an accumulated PUVA dose of 1000 joules/cm2 or more; another group of 389 patients, as the low-dose group, received 200 joules/cm2 or less. The occurrence of skin cancer in the two comparison groups is analyzed. RESULTS: In the high-dose group we observed an increased number of patients with squamous cell carcinoma, keratoacanthoma, and actinic keratosis. We did not see any patients with genital cancer, melanoma, or an increased number of patients with basal cell carcinoma. CONCLUSION: The risk of squamous cell carcinoma developing in patients who received a high dose of PUVA is confirmed. We speculate a combination of factors, including PUVA, may contribute to this risk.

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One hundred four psoriatic patients who had 8-methoxypsoralen-ultraviolet light A (PUVA) treatment between 1975-1987 were investigated to determine if skin cancer had ever occurred during or after the therapeutic period. Incidence data of skin cancer was applied to this group of patients to measure the expected number of patients with skin cancer. The significance of observed number versus expected of PUVA-treated patients with skin cancer was analyzed. The authors did not observe a significant increase of patients with skin cancer.

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During the period 1955-1959, approximately 4000 people in southeast Anatolia developed porphyria due to the ingestion of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. These HCB exposures subsequently led to the development of bullae on sun-exposed areas, hyperpigmentation, hypertrichosis, and porphyrinuria. The condition was called kara yara or "black sore." Many of the breast-fed children under the age of 2 years whose mothers had ingested HCB-treated grain died from a disease known as pembe yara or "pink sore." In this follow-up study of 252 patients, 20-30 years postexposure, there were 162 males and 90 females, with an average current age of 35.7 years, an average of onset of 7.6 years, and a duration of 2.2 years. Many patients had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include scarring of the face and hands (83.7%), hyperpigmentation (65%), hypertrichosis (44.8%), pinched facies (40.1%), painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 17 have at least one of the porphyrins elevated. A total of 56 specimens of human milk obtained from mothers with porphyria were analyzed for HCB. The average value was 0.51 ppm in HCB-exposed patients compared to 0.07 ppm in unexposed controls. Offspring of mothers with three decades of HCB-induced porphyria appear normal.

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Porphyria cutanea tarda (PCT) is the most frequently reported type of porphyria. The average patient is male more than 40 years old with a history of alcohol consumption. In women the incidence of PCT has increased with use of estrogens for birth control. The cutaneous features are those of chronic porphyrin photosensitivity on the light-exposed area of the skin: pigmentation, hirsuitism and fragility, and vesiculobullae, which has prompted the expression bullosa actinica et mechanica. One-third of the patients have glucose intolerance. PCT has been reported frequently among the Bantu people in South Africa as resulting from combinations of alcohol and cooking in ironware. The average patient has a higher than normal hematocrit, which is used as a guide to treatment by phlebotomy ranging from 8 to 14 units removed every 2-4 wk. Chemically induced PCT has been reported with chlorinated hydrocarbons, the best-known of which is hexachlorobenzene (HCB). Porphyria was noted in more than 3,000 patients in southeast Turkey between 1955 and 1961, because of consumption of seed wheat treated with HCB. In addition, more than 1,000 children under the age of 1 year died because HCB was transferred from the mother, either via the placenta or through breast milk.

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The efficacy of erythromycin base (E-Mycin tablets, 333 mg) and the efficacy of tetracycline hydrochloride (Panmycin tablets) were compared in this double-blind, randomized study. Two hundred patients with moderate to moderately severe acne vulgaris were randomly assigned to the study. One hundred patients received 1 gm of erythromycin base by mouth per day for 4 weeks, followed by 333 mg/day for 8 weeks, plus placebo for tetracycline. The second group of patients received 1 gm of tetracycline by mouth per day for 4 weeks, followed by 500 mg/day for 8 weeks, plus placebo for erythromycin. Both drugs reduced acne severity to the same extent. Pustules, papules, and open comedo counts decreased significantly over the 12-week period. Seventy-seven percent of the erythromycin-treated patients and 89% of the tetracycline-treated patients stated that their acne was markedly improved or improved by week 12. Most of the side effects in patients treated with erythromycin were gastrointestinal symptoms. Among the side effects in patients treated with tetracycline were Candida vaginitis in one patient and pseudotumor cerebri in one patient.

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The porphyrias can be grouped conveniently by their presenting symptoms. Acute intermittent neurological symptoms of neuritis, abdominal pain and psychoses may occur in acute intermittent porphyria, hereditary coproporphyria and variegata porphyria. Increase of the porphyrin precursors delta-aminolaevulinic acid and porphobilinogen may be observed in the urine during attacks (Watson-Schwartz test). Patients with acute symptoms of photosensitivity with burning pain and oedema within short exposure periods may have erythropoietic protoporphyria, with high erythrocyte and stool protoporphyrins, erythropoietic coproporphyria, and in the last few years of life the more recently described hepatoerythropoietic porphyria. Symptoms of chronic photosensitivity include; hyperpigmentation, hypertrichosis, easy fragility of the skin with bullae and subsequent scarring in porphyria cutanea tarda (PCT), with increased uroporphyrin in the urine and stool; variegate porphyria with increased protoporphyrin and coproporphyrin in the stool; congenital erythropoietic porphyria with an increased copro- and uroporphyrin (isomer I) in the erythrocytes, urine and stool; and hepatoerythropoietic porphyria in later life, in which the chronic features are similar to PCT. In 1913 Meyer-Betz injected himself with 200 mg haematoporphyrin. Initially, at the higher levels, the symptoms were those of solar urticaria as observed in erythropoietic porphyria, but after several months became identical to PCT. A comparison of quantitative porphyrin analysis (performed on 323 patients with porphyria) and chromatography provides additional confirmation for the diagnosis.

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Subchronic and chronic toxicities of hexachlorobenzene (HCB) were studied in both sexes of Swiss mice, Syrian golden hamsters and Sprague-Dawley rats, at dietary dosages of 0, 100 and 200 ppm (mice), and 0, 200 and 400 ppm (hamsters and rats) for 90 days. At day 91, 25/50 animals in each of 18 groups were killed for histology studies. The rest were killed at 6-week intervals until the study was ended. Marked hepatosplenomegaly, enlarged thymuses and lymph nodes, or swollen and granular-looking renal cortices with depressions or nodulary areas were commonly observed. Dose- and sex-dependent progressive changes included toxic-degenerative hepatitis, chronic cirrhosis, hepatomas, bile-duct adenomas and a few hepatocarcinomas in older animals. A generalized lymphohaematopoietic response led to thymic, splenic and nodal lymphosarcomas, especially in female mice. Toxic-tubular nephritis with cortical infarcts developed into regenerative foci and renal adenomas in low incidences. Liver lesions were more prominent in females, while renal changes were most common in male rats. HCB was retested in both sexes of rats at oral doses of 0, 75 and 150 ppm for up to 2 years. At the start, each group contained 94 rats, and four randomly selected rats were killed at weeks 0, 1, 2, 3, 4, 8, 16, 32, 48 and 64 for microscopy. Progressive liver lesions started as hyperaemia and degenerations (4 weeks), and developed into toxic hepatitis, cirrhosis and formation of pre- and neoplastic foci (36 weeks), with hepatomas, bile-duct adenomas and hepatocellular carcinomas (64 weeks) in very high incidences in females and renal adenomas in male rats.

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It has been estimated that during 1955-1959 in southeastern Turkey, approximately 4000 people developed porphyria due to ingestion of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. Patients subsequently developed bullae on sun-exposed areas, hyperpigmentation, hirsutism, weakness and porphyrinuria. Children born to mothers who had ingested the grain were exposed to HCB in maternal milk and transplacentally, resulting in the death of children under the age of two. In this follow-up study, 204 patients with a past history of HCB-induced porphyria were re-evaluated. There were 132 males and 72 females, with an average age of 32.1 years, an average age of onset of 7.1 years and a duration of 2.4 years. The clinical features of the 204 patients were: scarring of the face and hands in 86.7%, hyperpigmentation in 71.1%, hirsutism in 47.1%, pinched facies in 41.2%, fragile skin in 37.7%, painless arthritis in 66.6%, small hands in 64.2%, an enlarged liver in 4.4% and an enlarged thyroid in 37.3%; most patients also showed neurological symptoms. Urine and stool porphyrin levels were determined in all patients. Seventeen showed elevated levels of one of the porphyrins and eight were considered still porphyric after 25-30 years. A total of 56 specimens of human milk obtained from porphyric mothers were analysed for HCB. The average value was 0.51 ppm compared with 0.07 in controls. After HCB ingestion, abnormal porphyrin metabolism, dermatological, orthopaedic and neurological findings, and HCB residues in the milk of porphyric patients have been shown to persist at least for 25-30 years.

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During 1955-1961 in south-east Turkey, over 3000 patients developed porphyria due to ingestion of hexachlorobenzene, a fungicide added to wheat seedlings. Subsequently they developed pigmentation, hirsutism, weakness, porphyrinuria and bullae. The condition was called kara yara or 'black sore'. Many of the breast-fed children under the age of 1 year died from a disease known as pembe yara or 'pink sore'. In this follow-up study of 204 patients, 20-30 years later, there were 132 males and 72 females, average age 32.1 years (at time of examination), with an average age of onset of 10.2 years, and duration of 2.4 years. Neurological, dermatological, and orthopaedic abnormalities still persisted. Neurological symptoms included weakness (66%), paraesthesiae (54%), neuritis (63%), myotonia (49%), and occasional 'cogwheeling' (29%). Some individuals affected before puberty had small stature (44%), small hands (64%) and painless arthritis (67%). Severe residual scarring was common (85%), and pinched facies (42%), hirsutism (47%) and hyperpigmentation (71%) were also observed. Enlarged thyroids were observed in 37% (59% in females), which was above average of 5% in this area of Turkey. Porphyrin excretion, particularly uroporphyrin in the urine and stools, was still significantly increased in seventeen patients. Hexachlorobenzene levels as high as 2.8 p.p.m. were detected in human milk, and the average level (0.29 p.p.m. +/- s.d. 0.06) was 140 times the level allowed in cow's milk.

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Cutanea tarda and mixed porphyric symptoms resulted from accidental ingestion of hexachlorobenzene (HCB)-treated seed grain in Turkey 25 years ago and involved about 4,000 persons with a 10% mortality. Twenty-five years later, 161 patients, 63 women and 98 men, with histories of HCB exposure as children or young adults were studied. Many patients had persistent abnormal porphyrin metabolism and prominent neurological, dermatologic, and orthopedic symptoms and signs. Thyromegaly was seen in 60% of the women and 27% of the men. The children born to porphyric mothers 25 years ago all died of pembe yara secondary to maternal milk and transplacental transfer of HCB. Current lactation specimens of porphyric patients show high HCB levels, up to 3.12 ppm, but the infant offspring appear normal.

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The action spectra for producing minimal phototoxic erythema with topical 0.I% trimethyl psoralen (TMP) and 8-methoxypsoralen (8-MOP) were determined with a double monochromator in the range of 295-380 nm. both psoralens induced photosensitivity in the range of 313-365 nm; TMP was 54% more effective than 8-MOP. There was no difference in the dose needed to produce minimal UV erythema or phototoxic erythema with 8-MOP and TMP at 295 and 305 nm, but at 313 nm with 8-MOP, photosensitivity was enhanced 3.5 times, and with TMP, sensitivity was enhanced 5.5 times. The peak sensitivity with 8-MOP was at 330 nm and for TMP it was 335 nm. No photosensitivity occurred above 380 nm. Results suggest that TMP and 8-MOP are significantly photoreactive at 320-335 nm. Commonly used UV-A light sources show peak emission around 360 nm. If there is a relationship between development of erythema and therapeutic effectiveness than this raises the possibility of alternative UV light sources for phototherapy with psoralens.

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