A study of oil of bergamot and its importance as a phototoxic agent

It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.     

Successful treatment of resistant alopecia areata with a phototoxic dose of ultraviolet A after topical 8-methoxypsoralen application

Background: The efficacy of a phototoxic dose of ultraviolet A (UVA) after topical application of 8‐methoxypsoralen (8‐MOP) in the treatment of alopecia areata (AA) was evaluated previously in only one study. However, the possibility of spontaneous regrowth of hair cannot be excluded as sessions were carried out every 3 months. Objective: To determine the efficacy of a phototoxic dose of UVA after topical application of 8‐MOP in the treatment of AA resistant to other lines of treatment. Subjects/Methods: Thirty‐five patients with AA were treated by topical 8‐MOP application to the lesions followed by UVA irradiation using a phototoxic dose every 3 months for a maximum of four sessions. Severity grading of AA was carried out using the Severity of Alopecia Tool (SALT) score before and after treatment. Results: Fifty‐seven percent of patients showed a positive treatment response (40% showed complete and 17% showed partial response) with significant improvement of SALT score. The mean cumulative UVA dose was 22±8.3 J/cm². Mild reversible side effects were observed in 63% of patients after the first session. Conclusion: Phototoxic psoralen and ultraviolet A therapy after topical application of 0.1% 8‐MOP is an effective treatment option for resistant AA, with low total cumulative UVA dose, few treatment sessions, and minimal reversible side effects.     

A novel tetracationic phthalocyanine as a potential skin phototherapeutic agent

An amphiphilic tetracationic derivative of Zn(II)-phthalocyanine (RLP068) was prepared by means of chemical synthesis and was showed to possess efficient photophysical and photosensitizing properties against model biological substrates. RLP068 was incorporated into a gel formulation, which allowed its ready penetration into the epidermal layers, but not into the dermis, of both Balb/c and hairless SKH1 mice after 1-2 h of topical deposition. Pharmacokinetic studies showed that the phthalocyanine thus formulated does not enter the general blood circulation. The epidermis-associated amount of phthalocyanine was sufficient to cause an important cutaneous damage upon irradiation with red light (600-700 nm; 100-180 mW/cm(2), 160 J/cm(2)); the latter was confined to the epidermal area with no apparent diffusion to the underlying dermal layers or appearance of photosensitivity in distal skin areas. A systematic investigation of the interplay among the different parameters (deposition time of the formulated phthalocyanine on mouse skin, irradiation fluence rate and total light fluence) allowed us to identify the minimal phototoxic dose, as well as to define irradiation protocols allowing the repeatability of the phototherapeutic treatment. The potential of RLP068 to act as a PDT agent for cutaneous diseases is briefly discussed.     

Determination of the minimal phototoxic dose and colorimetry in psoralen plus ultraviolet A radiation therapy

BACKGROUND: The use of an adequate initial dose of ultraviolet A (UVA) radiation for photochemotherapy is important to prevent burns secondary to overdosage, meanwhile avoiding a reduced clinical improvement and long-term risks secondary to underdosage. The ideal initial dose of UVA can be achieved based on the phototype and the minimal phototoxic dose (MPD). The objective measurement of constitutive skin color (colorimetry) is another method commonly used to quantify the erythematous skin reaction to ultraviolet radiation exposure. The aim of this study was to determine variations in MPD and constitutional skin color (coordinate L(*)) within different phototypes in order to establish the best initial dose of UVA radiation for photochemotherapy patients. METHODS: Thirty-six patients with dermatological conditions and 13 healthy volunteers were divided into five groups according to phototype. Constitutional skin color of the infra-axillary area was assessed by colorimetry. The infra-axillary area was subsequently divided into twelve 1.5 cm(2) regions to determine the MPD; readings were performed 72 h after oral administration of 8-methoxypsoralen (MOP) followed by exposure of the demarcated regions to increasing doses of UVA. Results: The majority of the participants were women (73.5%) and their mean age was 38.8 years. The MPD ranged from 4 to 12 J/cm(2) in phototypes II and III; from 10 to 18 J/cm(2) in type IV; from 12 to 24 J/cm(2) in type V and from 18 to 32 J/cm(2) in type VI. The analysis of colorimetric values (L(*) coordinate) and MPD values allowed the definition of three distinctive groups of individuals composed by phototypes II and III (group 1), types IV and V (group 2), and phototype VI (group 3). CONCLUSIONS: MPD and L(*) coordinate showed variation within the same phototype and superposition between adjacent phototypes. The values of the L(*) coordinate and the MPD lead to the definition of three distinct sensitivity groups: phototypes II and III, IV and V and type VI. Also, the MPD values bear a strong correlation to coordinate L(*) values. Mean MPD values described for each of the three major sensitivity groups were higher than the values commonly used in clinical settings for the different phototypes. Therefore, phototype alone is not a good parameter to define the initial UVA dose. MPD and colorimetry could be used in pre-treatment evaluation of patients who are to be submitted to photochemotherapy, in a non-invasive and more accurate way when compared with the classical phenotype clinical criteria.     

Photosensitivity to lomefloxacin. A clinical and photobiological study

Photosensitivity is an uncommon but characteristic side effect of quinolones, with a variable incidence for the different drugs. Several cases, considered either phototoxic or photoallergic, have been described with lomefloxacin use. During the last 4 years we studied 8 patients (mean age 69.4 years) with eczematous or acute sunburn-like lesions in photo-exposed areas, after taking lomefloxacin for a period of one week to several months. After drug withdrawal and systemic and/or topical corticosteroids, lesions cleared within one week to two months, with dischromia in one patient. Six to eight weeks thereafter, a photobiological study was performed. Minimal erythema dose (MED) for UVA and UVB were normal and photopatch tests with lomefloxacin, ofloxacin, ciproflaxacin and norfloxacin, tested at 1%, 5% and 10% in petrolatum and irradiated with 5 and 10 J/cm2 UVA were negative in 7 patients and 20 controls. Patient 1 had a positive photopatch test with lomefloxacin. One patient, who inadvertently reintroduced the drug before photopatch testing, developed a sharply limited erythematous reaction at 48 h in all irradiated areas, without aggravation at the sites of the quinolones patches. Our patients illustrate the polymorphism of clinical photosensitivity to lomefloxacin and represent the largest series in which photobiological studies have been performed. As in previous reports there are arguments favouring photoallergy, but phototoxicity appears to be the main mechanism of photosensitivity to quinolones, particularly in older patients with concomitant diseases and long-term use of the drug.     

Kinetics and dose-response of photosensitivity in cream psoralen plus ultraviolet A photochemotherapy: comparative in vivo studies after topical application of three standard preparations

BACKGROUND: Topical photochemotherapy with bath psoralen plus ultraviolet (UV) A irradiation (PUVA) has been developed to reduce possible side-effects of oral PUVA therapy. Although the efficacy of bath PUVA therapy appears to be similar to oral PUVA therapy, provision of bathing facilities has obvious economic, logistic and sanitary implications. Cream PUVA therapy has recently been developed as a variation of topical PUVA. OBJECTIVES: To understand the photobiological effects and to increase the safety and effectiveness of this novel topical PUVA therapy, we assessed the kinetics and dose-response of phototoxicity of 8-methoxypsoralen (8-MOP) cream in order to develop a treatment schedule for this treatment option. METHODS: Ninety-eight patients (63 men and 35 women) undergoing cream PUVA therapy were studied. The phototoxic properties of topically applied 8-MOP in three different water-in-oil creams as vehicles were assessed. In a dose-response study, four concentrations of 8-MOP cream (0.0006-0.005%) were used for determination of the minimal phototoxic dose (MPD). The kinetics of photosensitization were tested by determination of MPDs after different application times of 8-MOP cream (10, 20, 30 and 60 min). The persistence of phototoxicity was assessed by UVA exposure at defined time intervals after application of 8-MOP cream (0, 30, 60 and 120 min). RESULTS: The concentration required to produce sufficient but not undue photosensitization of the skin was 0.001% 8-MOP. The duration of application leading to the lowest MPD was 30 min. Greatest photosensitization was achieved when UVA irradiation was performed between 0 and 30 min after 8-MOP removal. These findings showed no significant difference between the three vehicles used. CONCLUSIONS: Based on our data we recommend application of 0.001% 8-MOP in a water-in-oil cream for 30 min. Irradiation with UVA should be performed within 30 min after removal of 8-MOP cream, as there is a rapid decrease in photosensitivity thereafter.     

A study of the phototoxicity of lemon oil

Summary Lemon oil contains furocoumarin derivatives and is known to cause phototoxicity. In this study, lemon oil was fractionated, and its phototoxic activity was measured by means of a biological assay. The substances producing phototoxicity were identified by high-performance liquid chromatography as being oxypeucedanin and bergapten. The phototoxic potency of oxypeucedanin was only one-quarter of that of bergapten. However, the amounts of these two phototoxic compounds present in lemon oils produced in different regions of the world varied by a factor of more than 20 (bergapten, 4–87 ppm; oxypeucedanin, 26–728 ppm), and their ratio was not constant. The two compounds accounted for essentially all of the phototoxic activity of all lemon-oil samples. Among various other citrus-essential oils investigated, lime oil and bitter-orange oil also contained large amounts of oxypeucedanin. Oxypeucedanin was found to elicit photopigmentation on colored-guinea-pig skin without preceding visible erythema.     

PUVA treatment of alopecia areata totalis and universalis: a retrospective study

The results of PUVA treatment of alopecia areata (AA) totalis and universalis were reviewed in 26 adult patients. Eight of 15 patients with AA totalis and six of 11 patients with AA universalis achieved a complete response (>90% hair regrowth). Patients with AA totalis had a greater incidence of treatment failure (<25% hair regrowth) than those with AA universalis. Patients with a family history of AA were significantly less likely to have a positive response to PUVA than those with no family history. Sex, age at diagnosis and treatment, interval between diagnosis and treatment, and background of atopy were not significant determinants of outcome. Although unable to show significance for clinical response to treatment, this study demonstrates complete hair regrowth in patients with both AA totalis (53%) and universalis (55%) while reporting a low relapse rate among these patients (21%) within a long period of follow up (mean 5.2 years).     

Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol

BACKGROUND: There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24-83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity. OBJECTIVES: To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients. METHODS: Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients. RESULTS: Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17-79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting. CONCLUSIONS: When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.     

Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo

BACKGROUND: Recent advances in the pathophysiology of vitiligo have demonstrated defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may be involved in the regulation of melanin synthesis, and receptors for 1,25-dihydroxyvitamin D3 have been demonstrated on melanocytes. OBJECTIVES: We conducted an open study to determine the efficacy and tolerability of calcipotriol cream as monotherapy and in conjunction with psoralen plus ultraviolet A (PUVA) in the treatment of vitiligo. METHODS: Twenty-six patients with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and four were placed on combination treatment with twice-daily topical calcipotriol 50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three times weekly. RESULTS: Treatment was well tolerated at all sites and no adverse effects were reported. After a therapy time of 3-9 months (mean 6 months), 77% (17 of 22) of those treated with monotherapy showed 30-100% improvement, and three of the four patients on combination treatment showed good response. CONCLUSIONS: Topical calcipotriol appears to be an effective and well-tolerated treatment for vitiligo and can be safely used in conjunction with PUVA, but controlled studies are necessary to exclude the possibility of spontaneous repigmentation.     

Soluble oil dermatitis: a follow-up study

A pilot follow-up study of patients with soluble oil dermatitis was designed to investigate the effects on prognosis of aetiology and of stopping working with soluble oils. A questionnaire was sent to 121 machine operators who had been diagnosed over a 5-year period. Life table analysis of the 100 replies (83%) revealed a poor prognosis both for those who had continued to work with soluble oils and for those who had stopped. 78% (95% confidence intervals: 63%-94%) of those who continued to work with soluble oils had not healed 2 years after diagnosis. 70% (95% confidence intervals: 56%-83%) of those who stopped working with soluble oil had not healed 2 years after discontinuing contact. Both groups were divided into 4 subgroups with different combinations of aetiological components: allergic and endogenous, non-allergic and endogenous, allergic and non-endogenous, non-allergic and non-endogenous. No significant difference in outcome emerged in either the discontinued contact group or the continued contact group between any aetiological subgroups. Patients who discontinued contact with soluble oils fell into 2 groups: those who healed rapidly and those who developed a chronic dermatitis. 11 of the 15 patients who had healed after 2 years had done so within the first 3 months following cessation of contact. No factor could be identified to distinguish those with the more favourable prognosis. The implications of this study for the management of soluble oil dermatitis are discussed.     

A systematic study of the clinical and biochemical expression of variegate porphyria in a large South African family

BACKGROUND: Variegate porphyria (VP) is an autosomal dominant disorder associated with deficient haem synthesis. Recent reports indicate that the clinical penetrance of VP may have been overestimated in studies which predated the availability of DNA-based testing for VP. OBJECTIVES: To undertake a study specifically designed to assess the clinical and biochemical penetrance of VP in a kindred characterized by gene status. METHODS: We studied a large family carrying the South African founder mutation which is known to result in almost complete haplodeficiency. All informative members were tested for the R59W mutation. Biochemical evidence of porphyria was sought by porphyrin analysis and by plasma fluorescence scanning. The presence of clinically expressed porphyria was assessed using a structured questionnaire and telephone or personal interview. RESULTS: Of 62 informative subjects, 33 had inherited the mutation. Of 28 adults, one subject had experienced a single acute attack. She and a further 10 subjects had experienced photosensitivity. The frequency of acute attacks in this family is therefore 4% (95% confidence interval, CI 1-18%), and of photosensitivity is 39.3% (95% CI 24-58%). The sensitivity and specificity of porphyrin analysis in this family were 0.46 (95% CI 0.30-0.64) and 1.00 (95% CI 0.85-1.00), respectively, and for plasma scanning the values were 0.85 (95% CI 0.58-0.96) and 1.00 (95% CI 0.72-1.00), respectively. CONCLUSIONS: The clinical penetrance of VP in our family is approximately 40%. Many more subjects with VP are diagnosed in an asymptomatic phase than previously, and the acute attack is now an uncommon manifestation of VP. Plasma scanning is more sensitive than faecal porphyrin analysis, but neither is sufficiently sensitive for the detection of carrier status.     

Sesquiterpene lactone mix contact sensitivity and its relationship to chronic actinic dermatitis: a follow-up study

In a retrospective case note analysis over a 4-year period, 0.9% of all patients tested with a standard patch test series (65 of 7600) were demonstrated to have clinically relevant responses to a sesquiterpene lactone (SQL) mix. Of these patients, 11 (17%) also had a diagnosis of chronic actinic dermatitis. This group made up 25% of all patients diagnosed as suffering from CAD in this 4-year period. These figures differ somewhat from those reported by our group in an initial 4-year period immediately following the introduction of the mix into our standard patch test series, when 1.5% of all patients tested had a clinically relevant response to the SQL mix, including 36% of all patients with a diagnosis of CAD. It is not uncommon for the prevalence of sensitivity to an allergen to be overestimated immediately following its introduction into routine testing. Possible reasons for our findings are discussed.     

Chronic actinic dermatitis: A clinical study of 15 cases in northern Taiwan

BackgroundChronic actinic dermatitis (CAD) is an idiopathic photosensitive dermatosis induced by ultraviolet B (UVB), sometimes ultraviolet A (UVA), and occasionally visible light. Diagnosis is suggested by the clinical findings, typically a chronic eczematous rash on the sun exposed areas, and confirmed by phototesting, which demonstrates the abnormal photosensitivity. The aim of this study was to determine the characteristics of CAD in Taiwanese patients.MethodsWe retrospectively reviewed the clinical and photobiological features of all patients diagnosed as having CAD at our institute from 2002 to 2012.ResultsA total of 15 patients with CAD were identified. The mean age at diagnosis was 58.6 years (range, 28–82 years). All the patients were males. The face, neck, forearms, and dorsal hands were most commonly involved. Eight patients (53.3%) had decreased minimal erythema dose (MED) to both UVB and UVA; six patients (40.0%) had decreased MED to only UVB; one patient (6.7%) had decreased MED to only UVA. All were managed with photoprotection and topical corticosteroids. Four patients received azathioprine (50 mg twice a day to every other day) and one received prednisolone (10 mg per day to every other day).ConclusionIn Taiwan, CAD affects elderly men more commonly. The most common phototest results were decreased MED to both UVB and UVA, followed by to UVB alone. All patients were managed with photoprotection and topical corticosteroids, and some also required systemic agents, in particular azathioprine.     

A study evaluating ceftriaxone as a treatment agent for primary and secondary syphilis in pregnancy

OBJECTIVES: To evaluate the efficacy of ceftriaxone in pregnant women who were diagnosed with early syphilis. STUDY: Eleven women with a history of penicillin allergy, positive skin test, but prior history of safe usage of cephalosporins were included. Ceftriaxone (250 mg) was given intramuscularly once daily for 7 and 10 days to patients with primary and secondary syphilis, respectively. A second course of therapy was provided at 28 weeks' gestation. The rapid plasma reagin test (RPR) was measured before and after therapy. The blood of neonates was also tested at delivery and during the follow-up period. RESULTS: The serum RPR titers of 11 mothers decreased fourfold, 3 months after treatment. Ten patients developed negative RPR results. The serum RPR was negative at delivery or 6 months after delivery in all neonates. CONCLUSIONS: Ceftriaxone may be considered as an alternative for treatment of early syphilis in pregnancy.     

Photoepicutaneous testing UV-induced protection against photoxic reactions in normal and vitiliginous skin: A clinical and histological study

The effect of erythemic UV irradiation on the phototoxic reactions caused by topical methoxsalen + UVA exposure was studied on normal skin, normal-looking skin of vitiligo patients, and vitiliginous skin. Although only slight histological changes were detectable 9 days after irradiation with 5 MED of erythemic UV, this pre-irradiation did induce protection against photoxic reactions in all skin types. This protection was clinically equal in all skin types; the slight differences were not statistically significant. Histological evaluation, however, showed a most conspicuous protective effect on vitiliginous skin. In all skin types the influence of UV pre-irradiation was confined to epidermal protection; the dermal phototoxic changes were unaffected.     

Severe contact urticaria to guar gum included as gelling agent in a local anaesthetic

We report the first case of a life-threatening immediate-type hypersensitivity caused by Dynexan, a local anaesthetic gel. After mucosal application by his dentist, a 63-year-old man rapidly developed urticaria, dyspnea and, at last, he collapsed and remained unconscious for 2 hr despite emergency care. While the standard prick tests were negative to all local anaesthetics tested including lidocaine, a 1-fold positive reaction was detected to Meyprogat 60, an ingredient of Dynexan. As the gelling agent Meyprogat represents a derivative of guar (synonymous guar gum, guaran, E-412), we subsequently tested different guar products derived from Cyamopsis tetragonoloba beans and, as control, the closely related locust bean gum E-410. In the prick-to-prick tests, the guar-derived food additive Provigel NAG 905 provoked a 1-fold positive reaction. Native guar beans pounded and resuspended in water showed a 2-fold positive reaction, whereas no reaction was found to derivatives of locust bean gum. Specific immunoglobulin E were negative in all cases. Despite the common use of guar as versatile food additive or gelling agent, this is the first case of a severe immediate-type hypersensitivity after mucosal contact.     

Sensitizing and irritating properties of star anise oil

Star anise oil in 2 and 1% concentrations produced active sensitization in 5% of test subjects, and positive patch tests in 36 and 34%, respectively, of consecutive patients with dermatitis. A comparison of the results of tests with balsams and other essential oils showed that star anise oil does not give cross-reactions and pseudo cross-sensitivity. Patients positive to this oil are frequently positive to anethole and to other constituents of this oil: alpha-pinene, limonene and safrole. In tests with star anise oil it is noteworthy that a 1% concentration is strongly irritant, and 0.5% reveals sensitivity in only one fifth of the actively sensitized subjects. It is possible that the cause of false negative patch tests might be similar in the case of some other allergens.     

Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology

Since 1996, hyaluronic acid (HA) has been launched onto the market in Europe. Since then, different companies proposed their HAs. Biomatrix (NJ, USA) proposes an animal-derived HA (from rooster comb). Q-Med AB (Uppsala, Sweden) and LEA-DERM (Paris, France) are the main companies to have a nonanimal HA. HA is produced by bacterial fermentation from a specific strain of streptococci. HA has no species specificity and theoretically has no risk of allergy. No skin testing is necessary before injecting because HA is a biodegradable agent. To be utilized as a filler agent for improving wrinkles, scars, or increasing volumes, HA must be stabilized to obtain a sufficient half-life. Process of stabilization varies, according to each manufacturer. This explains the differences in longevity and in viscosity of the different products. Several HAs are suitable to fine lines, to deep wrinkles/folds, or to increase volume. A new indication for "rejuvenation" is injection into the superficial dermis and epidermis. The HA (stabilized or not) is not used to fill in but rather to hydrate and finally to rejuvenate the skin. This procedure must be repeated at intervals of a few weeks or months. If HA is the safest filler agent in cosmetic indications today, some rare side effects may appear and must be known to inform patients. Most of these complications are not severe and will disappear when the product is degraded.