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Background: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations., Objective: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort., Methods: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases., Results: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P < .0005 for both), whereas the mean age of onset was earliest in GPP (31.0 vs 43.7 years in PPP and 51.8 years in ACH, P < .0001 for both). The percentage of female patients was greater in PPP (77.0%) than in GPP (62.5%; P = 5.8 × 10 -5 ). The same applied to the prevalence of smokers (79.8% vs 28.3%, P < 10 -15 ). Although AP1S3 alleles had similar frequency (0.03-0.05) across disease subtypes, IL36RN mutations were less common in patients with PPP (0.03) than in those with GPP (0.19) and ACH (0.16; P = 1.9 × 10 -14 and .002, respectively). Importantly, IL36RN disease alleles had a dose-dependent effect on age of onset in all forms of pustular psoriasis (P = .003)., Conclusions: The analysis of an unparalleled resource revealed key clinical and genetic differences between patients with PPP and those with GPP., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Polymorphic light eruption (PLE) is the most common idiopathic photodermatosis. Reactive oxygen species have been implicated in the pathogenesis of PLE. Polypodium leucotomos (PL) is a natural extract from tropical fern leaves with potent antioxidant and anti-inflammatory properties., Objective: In this study we sought to evaluate whether a concentrated hydrophilic extract of PL might prevent or delay the photoinduction of typical PLE lesions by artificial ultraviolet (UV) radiation., Methods: A total of 35 patients with long-standing PLE were included in this open, uncontrolled bicenter study. PLE was induced by photoprovocation with artificial UVB and UVA light, thereafter oral treatment with PL was initiated. Two weeks later a second photoprovocation was performed while the patients were still taking PL., Results: Thirty patients developed PLE lesions after repeated irradiation with UVA. Of these, 18 patients also responded to UVB. After PL treatment, 9 (30%) and 5 (28%) patients, respectively, were unresponsive to repeated UVA and UVB exposure. In the remaining patients, the mean number of UVA and UVB irradiations required to elicit PLE increased significantly from 1.95 to 2.62 (P = .005) and from 2.38 to 2.92 (P = .047), respectively., Limitations: The study was open and uncontrolled and included a relatively small number of patients., Conclusion: Our data indicate that oral PL treatment might be beneficial for the prevention of PLE., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Recent studies suggest that ultraviolet (UV) A1 phototherapy is an effective treatment for localized scleroderma (LS); however, the optimum UVA1 dose remains to be determined., Objective: We sought to compare the immediate and long-term efficacy of low- versus medium-dose UVA1 phototherapy for plaque-type LS., Methods: Three comparable plaques in 16 patients were treated with 20 J/cm2 UVA1, 70 J/cm2 UVA1, or no irradiation. In total, 30 treatments were given. Skin thickness was determined by high-frequency ultrasound examination and clinical scoring. Assessments were done at baseline, immediately after treatment, and 3, 6, and 12 months thereafter., Results: Ultrasound measurement showed a significantly greater reduction of skin thickness with 70 J/cm2 than with 20 J/cm2 at all time points of the study except immediately after UVA1 treatment. The clinical score of the irradiated plaques also decreased substantially but failed to detect a significant difference between the two dose regimens., Limitations: Our results only pertain to plaque-type LS and are limited by a small sample size., Conclusion: Medium-dose provides for better long-term results than low-dose UVA1 in LS as shown by ultrasound assessment. With clinical scoring, no significant difference between the two UVA1 dose regimens was detected, indicating that ultrasound measurement is a more sensitive method for quantifying treatment-induced skin changes in patients with LS.

Background: Bath-psoralen plus ultraviolet A (PUVA) radiation therapy is increasingly replacing oral PUVA because of its superior short- and long-term safety profile. Several investigations in recent years have led to a refinement of the bath-PUVA protocol; however, the optimal therapeutic concentration of methoxsalen in the bath water has as yet not been delineated., Objectives: The therapeutic efficacy and tolerability of bath-PUVA by using two different dilutions of methoxsalen (1 mg/L vs 5 mg/L or 0.0001% vs 0.0005%) were compared in 46 patients with chronic plaque-type psoriasis in a prospective, randomized, double-blind study., Methods: Scores of the Psoriasis Area and Severity Index excluding psoriasis of the head (PASI(TUL)) and the Plaque Severity Index (PSI) were assessed at baseline and at biweekly intervals thereafter until (near)complete clearance or maximal improvement. In addition, methoxsalen plasma levels were determined immediately after the psoralen bath during the first week of treatment and treatment-related side effects were recorded throughout the entire study period., Results: The median baseline PASI(TUL) score decreased from 11.7 (7.5-32.8) to 3.3 (0.6-1.2) (-72%) in the 1 mg/L methoxsalen group and from 10.8 (6.6-20.7) to 1.4 (03.2) (-87%) in the 5 mg/L methoxsalen group (P < .01). The median baseline PSI score decreased from 9 (6-12) to 3.1 (0.6-10) (-66%) in the 1 mg/L methoxsalen group and from 9.3 (7.3-12) to 1.6 (0-3.6) (-83%) in the 5 mg/L methoxsalen group (P < .01). The median cumulative UVA exposure dose was 25.4 (5.3-81.5) J/cm2 for 5 mg/L methoxsalen and 71.9 (20.7-587.3) J/cm2 for 1 mg/L methoxsalen (P = .001). The number of exposures (22 [11-29] vs 23 [11-34]) and treatment duration (43 [19-68] vs 44 [23-66] days) was comparable for both methoxsalen dilutions (P = .97). Median psoralen plasma levels were 0 (0-26) ng/mL after the 1 mg/L and 30 (0-64) ng/mL after the 5 mg/L methoxsalen immersion (P = .001). Mild to moderate adverse events were more common in the 5 mg/L methoxsalen group., Limitations: The conclusions of this randomized controlled study are limited by the relatively small sample size., Conclusions: Our data indicate that in bath-PUVA treatment the use of a high (5 mg/L) methoxsalen concentration is substantially more effective in clearing chronic plaque-type psoriasis than a low (1 mg/L) concentration.

Background: Topical 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) has been established in recent years as an effective treatment for disseminated actinic keratosis (AK). As yet, however, data are lacking to define the optimal light dose for activation of ALA-induced protoporphyrin IX in AK., Objective: In the present study our purpose was to compare the efficacy and tolerability of 3 different doses of red light for ALA-PDT of AK., Methods: Twenty-seven patients with at least 3 clearly definable, mild or moderate AKs on the scalp or face entered the study. After occlusion for 4 hours with 20% ALA, one AK each was irradiated at random with a single dose of 70, 100, or 140 J/cm2. PDT-induced pain was assessed by the patients by means of a visual analog scale that graded pain intensity between 0 and 10. Follow-up examinations were performed 1 and 3 months after PDT., Results: One month after PDT, the rate of complete remission (CR) was 89% for 70 J/cm2, 92% for 100 J/cm2, and 81% for 140 J/cm2. The CR rates at 3 months were 81% for 70 J/cm2, 77% for 100 J/cm2, and 69% for 140 J/cm2. No significant difference in therapeutic efficacy was found among the 3 light doses at either 1 month (P = .36) or 3 months (P = .96) after PDT. The degree of PDT-induced pain during irradiation was substantial and not statistically different (P = .06) for all 3 light doses., Limitations: The conclusions from this study are limited by the small sample size and only apply to topical ALA-PDT., Conclusion: Our results indicate that a red light dose of 70 J/cm2 may be sufficient for effective topical ALA-PDT of disseminated, mild to moderate AK on the face and scalp.

Background: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK., Objective: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs., Methods: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2))., Results: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy., Conclusion: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.

A 44-year-old female British travel guide suddenly had fever, nausea, vomiting, and diarrhea develop during her stay in South India. Four days later she was transported to our hospital. At admission she had a high temperature, impaired respiration, and abdominal pain. Clinical examination revealed bilateral pleural effusion, hepatomegaly, and ascites. Two days later the patient showed a generalized macular rash with a conspicuous sparing of small islands of normal skin. Hemorrhagic erythema on the palms and soles as well as focal petechiae on the hard palate and scleral and conjunctival bleeding were also observed. Hypotension and renal insufficiency developed 1 week after the illness started. Laboratory investigations revealed highly elevated levels of hepatic enzymes, severe hemolytic anemia, decreased platelet counts, and abnormal coagulation values. The presumptive clinical diagnosis of dengue hemorrhagic fever was supported by serologic testing that disclosed sustained high titers of hemagglutination inhibition antibodies. Symptomatic therapy with substitution of volume and albumin, blood transfusions, and administration of antipyretics resulted in complete recovery within 6 weeks.

Background: Several studies have demonstrated the efficacy of UVA1 (340-400 nm) phototherapy for patients with severe atopic dermatitis. However, the optimum treatment dose has yet to be determined. Although in seminal investigations high UVA1 doses were used, comparable results were reported in recent studies with a medium-dose regimen., Objective: Our purpose was to compare the efficacy of high-dose with medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis., Methods: Ten adult patients with a median baseline SCORAD score of 67 were enrolled in an investigator-blinded, bilateral comparison study. Treatment was given 5 times weekly over a period of 3 weeks on an outpatient basis. Irradiation was performed by exposing one half of the patient's body to high-dose UVA1 (< or =130 J/cm(2)), and the contralateral body side received only half that dose. The clinical response was assessed after 5, 10, and 15 treatments. After completion of the study, patients were followed up for 6 months to evaluate the duration of clinical improvement., Results: All but one patient responded favorably to treatment. High-dose UVA1 led to a decrease of the median SCORAD score by 33.4% after 1 week, 38.4% after 2 weeks, and 34.7% after 3 weeks. The respective values for the medium-dose regimen were 29.7%, 36.4%, and 28.2%. The difference in efficacy between the two dosages remained below the level of significance at all time points. Relapses occurred after a median of 4 weeks. Time of onset and severity of relapse were the same for both doses., Conclusion: Our data support previous uncontrolled observations that medium-dose UVA1 is comparably as effective as high-dose treatment for patients with severe generalized atopic dermatitis. Irrespective of the dose regimen, follow-up examinations revealed early relapse in the majority of patients.

Background: Oral corticosteroid pulse therapy has provided inconsistent results in the treatment of Indian patients with vitiligo., Objective: We wanted to evaluate the efficacy, safety, and tolerability of oral dexamethasone pulse therapy in a cohort of Austrian patients with vitiligo., Methods: Twenty-nine patients with vitiligo were included in the study. Of these, 25 had progressive and 4 had stable disease. The patients were given weekly pulses of 10 mg dexamethasone each on 2 consecutive days followed by 5 days off treatment for a maximum period of 24 weeks. Clinical response and side effects were evaluated in monthly intervals. Plasma cortisol and corticotropin levels were monitored before and up to 6 days after the dexamethasone pulse in the first and fourth week of treatment in 14 patients., Results: After a mean treatment period of 18.2 +/- 5.2 weeks, the disease activity was arrested in 22 of 25 patients (88%) who had active vitiligo before the study. Marked repigmentation occurred in 2 patients (6.9%) and moderate or slight repigmentation in 3 patients (10.3%) each. No response was noted in 21 patients (72.4%). Side effects were recorded in 20 patients (69%) and included weight gain, insomnia, acne, agitation, menstrual disturbance, and hypertrichosis. Plasma cortisol and corticotropin values were markedly decreased 24 hours after the second dexamethasone dose, yet returned to baseline values within the off treatment period before the next dexamethasone pulse., Conclusion: Our data show that oral dexamethasone pulse treatment is effective in arresting progression of vitiligo yet fails to induce satisfactory repigmentation in the great majority of our patient cohort. Mild to moderate side effects are common with this treatment modality; however, sustained suppression of endogenous cortisol production does not occur with the pulse regimen.

Background: Bath-PUVA treatment, originally established in Scandinavia, offers several advantages over oral PUVA and has become increasingly popular in recent years. Outside Scandinavia 8-methoxypsoralen (8-MOP) is the prevailing photosensitizer for this PUVA modality and is used arbitrarily in a wide range of concentrations. Up to the present, data are lacking on the impact of 8-MOP bath-water concentration on UVA dosimetry., Objective: We investigated the influence of increasing 8-MOP bath-water concentrations on photosensitivity in bath-PUVA treatment., Methods: Fifteen healthy volunteers without abnormal photosensitivity or recent exposure to ultraviolet radiation were included in an intraindividually controlled comparison study. In all volunteers the minimal phototoxic dose (MPD) was determined on the volar side of their forearms after immersion for 20 minutes in 4 different 8-MOP bath-water concentrations (0.5, 1, 2.5, and 5 mg/L). The correlation between 8-MOP concentration and photosensitivity (defined as the reciprocal value of the MPD) was analyzed by linear regression analysis. In addition, the time course of erythema formation and the UVA dose-erythema response curve was assessed for each psoralen concentration., Results: The median MPD and the 25%-75% interquartile were 5.7 J/cm(2) (5.7-8), 4 J/cm(2) (4-5.7), 2.8 J/cm(2) (2.8-5.7), and 2 J/cm(2) (2-2.8) at an 8-MOP concentration of 0.5, 1, 2.5, and 5 mg/L, respectively. Linear regression analysis revealed a significant correlation between 8-MOP bath-water concentration and photosensitivity (r = 0.98; P =.019). Bath-PUVA-induced erythema peaked after a median time interval of 3 days, with a range of 2 to 4 days. The slope of the UVA dose-erythema response curve was similar for all psoralen concentrations., Conclusion: UVA dose requirements in bath-PUVA treatment decrease linearly with increasing 8-MOP concentrations. A single MPD assessment at 72 hours after the UVA exposure is inappropriate for accurate determination of the patients' photosensitivity. The hazard of wrong UVA dosimetry is comparable at all psoralen concentrations.

Background: Early American and European multicenter trials on the efficacy of photochemotherapy (PUVA) for psoriasis have clearly shown that the treatment protocol has a crucial impact on the cumulative UVA dose required for clearing patients. Most, if not all, treatment protocols rely on the PUVA-induced erythema as a guideline for UVA dosimetry., Objective: Our aim was to investigate whether phototoxic erythema is integral to an optimized PUVA protocol or reflects an unnecessary overexposure of patients., Methods: A standard high-dose UVA regimen using minimal phototoxic doses (MPD) was compared against two different low-dose regimens. To this purpose a bilateral comparison study was performed on 31 patients and divided in two parts. In the first trial on 14 patients, half of each patient's body was irradiated at each visit with 1 MPD, whereas the other half received only two thirds of the MPD. In the second trial on 17 patients treatment with 1 MPD was compared against treatment with one half of the MPD., Results: A total of 27 patients (12 patients in the first trial, 15 patients in the second trial) completed the study. In both trials the suberythemogenic doses were therapeutically as effective as the minimal phototoxic doses., Conclusion: We conclude that PUVA-induced erythema is not a prerequisite for effective psoriasis treatment and that a low-dose UVA regimen is a promising approach to increase the short- and long-term safety of photochemotherapy.

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.

Two hundred ninety-seven long-term photochemotherapy (PUVA)-treated patients from an original cohort of 418 subjects reported in 1980 were reevaluated in a second follow-up in order to determine the risk of tumor development under long-term PUVA. Within an observation period of up to 8 years (mean, 63.1 months) six patients with squamous cell carcinomas and three with basal cell carcinomas were observed. Eight of the nine tumor patients had been exposed to potential carcinogens such as arsenic and/or ionizing radiation prior to PUVA treatment. Five with squamous cell carcinomas were skin type I or II; in four of the six patients with squamous cell carcinomas the tumors were located on unexposed skin areas. The mean cumulative ultraviolet A (UVA) dose in three of the six squamous cell carcinoma patients was three times as high as that in the group of nontumor patients. The other three squamous cell carcinoma patients had lower mean doses than nontumor patients, as did the three patients with basal cell carcinomas. Although the cumulative UVA dose may eventually turn out to be relevant for PUVA carcinogenesis, our present data do not sufficiently substantiate a correlation between cumulative UVA dose and squamous cell carcinoma formation in PUVA-treated patients. This report confirms that previous exposure to carcinogens appears to be the most important factor for nonmelanoma skin tumor formation in long-term PUVA patients.

In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.

Twenty-eight patients with vitiligo were treated with a new photochemotherapeutic regimen using khellin, a furanochromone, as photosensitizer, together with ultraviolet A (UVA) irradiation. Twenty-five patients received khellin orally and three patients were treated with topical khellin. Treatments were given three times weekly. As opposed to psoralens, khellin did not induce skin phototoxicity with UVA but it induced repigmentation similar to psoralens. The treatment success strongly depended on the number of treatments. More than 70% repigmentation was achieved in 41% of the patients who had received 100 to 200 treatments. This success rate is comparable to the rate obtained with psoralens. Seven patients experienced a mild elevation of liver transaminases within the early treatment phase and their treatments were discontinued. No long-term internal organ or skin toxicity was observed. The major advantage of khellin is that it does not lead to phototoxic skin erythema and thus can be considered safe for home treatment. Because of its photochemistry it may be considered less hazardous than psoralens regarding mutagenicity and carcinogenicity.

Polymorphous light eruption is a common seasonal photodermatosis with a typical history and clinical picture. In the interval, when no lesions are present, the diagnosis relies on artificial reproduction of polymorphous light eruption by phototesting. Photochemotherapy (psoralens with ultraviolet A [PUVA]) is currently an effective preventive treatment. One hundred sixty-seven patients with either a history of polymorphous light eruption or manifest disease entered our study. Of 142 patients tested, 49% developed typical lesions of polymorphous light eruption at the test sites. In 56% the action spectrum was found to be in the ultraviolet A range, in 17% in the ultraviolet B range, and in 26% in both ranges. A total of 122 patients received preventive treatment with PUVA. Of these, fifty-one returned for follow-up. Of the patients who were followed up, 64% reported total protection during outdoor activities in the summer, 26% reported partial protection, and 10% were not protected. Failure to improve was unrelated to the action spectrum. The action spectrum and the incidence of positive results on phototests in our patient population differed from those reported by others. It is possible that differences in the test protocols and in the light sources used may account for this discrepancy. There is clearly a need for a standardized test procedure. However, the majority of patients benefit from PUVA pretreatment regardless of their action spectrum.