A 25-Hour Fast Among Quiescent Hereditary Coproporphyria and Variegate Porphyria Patients is Associated With a Low Risk of Complications.

OBJECTIVE: In patients with acute hepatic porphyria (AHP), prolonged fasting is a known trigger of AHP attacks. Despite this, some Jewish AHP patients-mainly hereditary coproporphyria (HCP) and variegate porphyria (VP) patients-fast for 25 consecutive hours during the traditional Jewish holy day known as Yom Kippur. In this study, we evaluated the effect of the fast on these patients. METHODS: A retrospective study and survey of AHP patients in Israel was carried out. Patients were asked whether they have fasted and whether any symptoms were induced by this fast. Patients' medical records were reviewed for an emergency department (ED) visit following Yom Kippur between 2007 and 2019. Only 3 acute intermittent porphyria (AIP) patients reported fasting; they were excluded from analysis. RESULTS: A total of 21 HCP patients and 40 VP patients completed the survey; 30 quiescent patients reported they fast, while 31 did not fast. The majority of fasting patients (96.67%) reported no symptoms following a fast. We found no statistically significant association between ED visits 1 week (0.26% in both fasting and non-fasting patients) or 1 month (2.1% visits in non-fasting versus 0.78% in fasting patients) following Yom Kippur. Of the symptomatic ED visits following a fast, none were defined as severe attacks. CONCLUSION: A 25-hour fast in stable HCP and VP patients did not increase the risk of an acute attack and can probably be regarded as safe.

Paradoxical Hypertrichosis Associated with Laser and Light Therapy for Hair Removal: A Systematic Review and Meta-analysis.

BACKGROUND: Paradoxical hypertrichosis (PH) is an uncommon, poorly understood adverse effect associated with laser or intense pulsed light treatment for hair removal. OBJECTIVE: The objective of this study was to conduct a systematic review and meta-analysis to determine PH prevalence and associated risk factors. METHODS: We conducted a systematic review and meta-analysis of studies evaluating hair removal with lasers or intense pulsed light. Primary outcome was PH prevalence. Meta-regression and subgroup analysis were used to investigate associations among treatment modality, patients' characteristics, and PH. RESULTS: Included were 9733 patients in two randomized controlled trials and 20 cohort studies (three prospective and 17 retrospective). Pooled PH prevalence was 3% (95% confidence interval 1-6; I2 = 97%). Paradoxical hypertrichosis was associated with a face or neck anatomic location, and occurred in only 0.08% of non-facial/neck cases. Treatment modality and interval between treatments had no effect on the PH rate. There were insufficient data to determine the association between sex and skin type to PH. In three out of four studies, PH gradually improved with continued therapy. CONCLUSIONS: Based primarily on cohort studies, PH occurs in 3% of patients undergoing hair removal with lasers or intense pulsed light, yet rarely outside the facial/neck areas. Treatment modality does not seem to be a contributing factor. Continuation of treatment in areas with PH may be the most appropriate treatment.

Inherited genetic late-onset erythropoietic protoporphyria: A systematic review of the literature.

BACKGROUND: Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at any age, even during adulthood, and is associated with hematological disorders. A third, less-studied type of EPP is also inherited but appears later in life (during adulthood). PURPOSE: To evaluate the characteristics of inherited genetic late-onset (IGLO) EPP. METHODS: A systematic comprehensive search of the literature was conducted using PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases. Studies describing patients with IGLO EPP were included. Additionally, we present an index case of a patient, treated at our clinic in whom inherited genetic EPP was diagnosed at age 21 years. RESULTS: The search yielded 1514 citations. Five publications were eligible for review. Along with our case, 7 patients (4 males) were included in the analysis. Mean age at disease onset was 34.2 years (range 18-69, median 30). Most patients presented with mild pruritus and rash in a photosensitive distribution. Mean level of free erythrocyte protoporphyrin IX (FEP) was 8.6 µmol/L. A mutant ferrochelatase gene (FECH) in trans to a hypomorphic FECH allele was found in 3 of the 4 patients who underwent genetic testing. CONCLUSION: We describe the distinct features of IGLO EPP. This work emphasizes that a diagnosis of inherited genetic EPP should not be ruled out in adults with new-onset photosensitive manifestations.

Does interval time between pulsed dye laser treatments for port-wine stains influence outcome? A systematic review and meta-analysis.

The pulsed dye laser (PDL) is the standard treatment for port-wine stains (PWS). Maximal improvement occurs after multiple treatment sessions; however, the optimal treatment interval has yet to be determined. The aim of this study was to review whether there is an association between PDL treatment interval and outcome of PWS. Six databases were searched by three reviewers for publications investigating treatment of PWS with PDL. The 75% improvement rates (75IR) were extracted for quantitative analysis. Meta-regression was used to investigate the association between treatment intervals and 75IR. The systematic review included 1 RCT and 33 cohort studies (7 prospective cohorts and 26 retrospective cohorts), with a total of 3777 patients. The pooled 75IR was 37% (95% CI 29-45%; I2 = 95%). Light Fitzpatrick skin type (p = 0.04), facial anatomic location (p = 0.01), and young age (p = 0.008) were associated with 75IR. In an unadjusted (p = 0.42) and multivariable adjusted (p = 0.98) meta-regression, no association was found between time interval between treatments and 75IR. These results persisted in a sensitivity analysis of studies with a mean patient age of ≤ 1. The majority of included studies were heterogeneous and retrospective. Based on cohort studies of low-to-moderate quality, time intervals between PDL treatments are not associated with PWS outcome.

Greater disease burden of variegate porphyria than hereditary coproporphyria: An Israeli nationwide study of neurocutaneous porphyrias.

Hereditary coproporphyria (HCP) and variegate porphyria (VP) are referred to as neurocutaneous porphyrias (NCP). Data concerning their systemic presentation are limited and no direct attempt of comparison of the two has ever been made. Our aim was to describe the type and frequency of systemic manifestations of NCPs in Israeli patients. A cross-sectional survey was conducted. The study population included all patients with NCP diagnosed at the Israeli National Service for Biochemical Diagnoses of Porphyrias (INSP) between 1988 and 2019. Of the 83 patients with NCP who were alive in 2019, 61 (73%) completed the survey, 40 with VP and 21 with HCP. Systemic symptoms were reported by 63% of the VP group and 62% of the HCP group (p = .96); corresponding rates of cutaneous symptoms were 58% and 5% (p < .001). We found no association between the occurrence of systemic and cutaneous symptoms. Among patients with systemic involvement, abdominal pain was the predominant systemic symptom, found in 64% of the VP group and 69% of the HCP group; Analysis of symptom frequency showed that in 68% of the VP group, systemic symptoms (either abdominal, musculoskeletal or neuropsychiatric) occurred on a daily/weekly basis, whereas the HCP group experienced less than one symptom per week (p < .001). This nationwide study depicts a significantly heavier disease burden in VP patients compared to HCP owing to its more frequent neurovisceral and cutaneous manifestations.

Laser Treatment for Non-Melanoma Skin Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Surgery is the mainstay of treatment for non-melanoma skin cancer. Lasers are an additional option. OBJECTIVE: The objective of this study was to review the literature on the efficacy and safety of lasers for the treatment of non-melanoma skin cancer. METHODS: A systematic review and meta-analysis of laser treatment for non-melanoma skin cancer was performed. The primary outcome was recurrence rate (RR). RESULTS: The review included 32 studies (six randomized controlled trials and 26 cohort studies): 27 evaluated basal cell carcinomas (BCCs), three squamous cell carcinomas, and two both, for a total of 4755 BCCs and 214 squamous cell carcinoas. Most BCCs were low risk. The Nd:YAG laser (seven studies, 3286 BCCs) had a 3.1% RR (95% confidence interval [CI] 1.4-6.4%) during a mean follow-up of 7.9 years, with a low rate (< 20%) of scarring and dyspigmentation. The CO2 laser (ten studies, 904 BCCs) had a 9.4% RR (95% CI 4.1-20) during a mean follow-up of 2.1 years, with a low rate of side effects. The pulsed dye laser (eight studies, 206 BCCs) had a 38% RR (95% CI 24-55). In two studies, the Nd:YAG laser demonstrated a RR of 10% (95% CI 2-31) for Bowen's disease, and in three studies, the CO2 laser demonstrated a RR of 22% (95% CI 5-61) for squamous cell carcinoma. CONCLUSIONS: Based on cohort studies, the Nd:YAG laser is a safe and efficacious modality for the treatment of low-risk BCC. Based on settings applied in prior studies in the literature, the CO2 laser is less efficacious than the Nd:YAG laser, thus it cannot be recommended for BCC treatment. Insufficient data preclude conclusions regarding laser treatment for squamous cell carcinoma. REGISTRATION: PROSPERO registration number CRD42019129717.

Clinical features of genetic cutaneous porphyrias in Israel: A nationwide survey.

BACKGROUND: There are three major types of genetic cutaneous porphyrias (GCP): erythropoietic protoporphyria (EPP), variegate porphyria (VP), and hereditary coproporphyria (HCP). Scarce data are available regarding their impact on patients' quality of life in the Mediterranean region. PURPOSE: To describe the cutaneous features of GCP in Israel. METHODS: An established nationwide cohort of patients with GCP diagnosed during 1988-2019 was surveyed by telephone for cutaneous features of GCP. Impact on quality of life was assessed using the Dermatology Life Quality Index. RESULTS: Of the 95 patients with GCP, 71 (75%) completed the survey (21 HCP; 40 VP; 10 EPP). All EPP patients reported cutaneous symptoms compared with 58% of VP and 5% of HCP (P < .001). Mean age at symptom onset was 7 ± 6 years in EPP and 25 ± 15 years in VP (P < .001). Photosensitivity was the most common symptom in EPP (90%). In VP photosensitivity (52%), blistering (52%) and scarring (74%) were all common symptoms. In both VP and EPP, the dorsal hands/forearms were the most affected regions (≥96%), and in ≥ 78%, symptoms occurred on an almost daily basis. All EPP patients changed their lifestyle due to cutaneous symptoms vs 57% in VP. Major effect on quality of life was observed among EPP patients compared with a moderate effect in VP. No treatment was effective in EPP, while phototherapy and moisturizers were effective in 5 of 7 (71%) VP patients. CONCLUSION: This study sheds light on the cutaneous features of the GCP, which have a substantial effect on patients' quality of life.

Nonsurgical Treatments for Extramammary Paget Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD); however, nonsurgical approaches have gained popularity in recent years. OBJECTIVES: To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. METHODS: A systematic review and meta-analysis of nonsurgical EMPD treatments was performed. The primary outcome was complete response (CR); secondary outcomes were clinical regression by ≥50%, adverse events, and recurrence rate. RESULTS: The systematic review included 43 observational studies (341 patients; 7 prospective cohort studies, 19 retrospective cohort studies, and 17 cases series) evaluating 5 treatment modalities. Imiquimod (13 studies, 110 patients) administered at variable doses ranging from daily to twice weekly for 2-56 weeks demonstrated CR of 54% (95% CI, 40-67%; I2 = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22-53%; I2 = 52%) of patients achieved CR. Radiotherapy (12 studies, 67 patients) showed CR of 97%, but was associated with local and systemic side effects. Ablative lasers and topical fluorouracil and calcipotriene lacked adequate evidence of efficacy. CONCLUSIONS: Imiquimod and radiotherapy are the most appropriate nonsurgical modalities for EMPD treatment given their good efficacy and safety profile. PDT has limited efficacy but may be appropriate in selected clinical settings.

Acquired erythropoietic protoporphyria: A systematic review of the literature.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a semi-dominantly inherited porphyria presenting with photosensitivity during early childhood. Acquired EPP has been reported; however, data regarding this rare disorder are scarce. PURPOSE: To evaluate the characteristics of acquired EPP. METHODS: A comprehensive search of PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases was performed by three reviewers. Studies describing patients with acquired EPP were included. Additionally, we present an index case of a 26-year-old patient who acquired clinically and biochemically typical EPP in association with myelodysplastic syndrome (MDS). RESULTS: We included 20 case reports describing 20 patients. Most (80%) patients were male of mean age 58 ± 13 years. In all patients, acquired EPP was associated with hematological disease, most commonly MDS (85%) followed by myeloproliferative disease (10%). In 86% of cases, hematological disease led to abnormality or somatic mutation in chromosome 18q (the locus of the ferrochelatase gene). The mean erythrocyte protoporphyrin IX concentration was very high (4286 µg/dL). Most (90%) patients presented with photosensitivity, 20% experienced blistering, and 25% presented with hepatic insufficiency, both uncommon in EPP. In 55% of patients, hematological disease was diagnosed after occurrence of cutaneous symptoms. Beta-carotene led to partial control of symptoms in 5 patients and resolution in another patient. Azacitidine treatment of MDS led to resolution of cutaneous symptoms in three patients. CONCLUSION: We present the distinct features of acquired EPP and highlight that any patient presenting with new-onset photosensitivity, irrespective of age should be evaluated for porphyria.

Blind separation of time/position varying mixtures.

We address the challenging open problem of blindly separating time/position varying mixtures, and attempt to separate the sources from such mixtures without having prior information about the sources or the mixing system. Unlike studies concerning instantaneous or convolutive mixtures, we assume that the mixing system (medium) is varying in time/position. Attempts to solve this problem have mostly utilized, so far, online algorithms based on tracking the mixing system by methods previously developed for the instantaneous or convolutive mixtures. In contrast with these attempts, we develop a unified approach in the form of staged sparse component analysis (SSCA). Accordingly, we assume that the sources are either sparse or can be "sparsified." In the first stage, we estimate the filters of the mixing system, based on the scatter plot of the sparse mixtures' data, using a proper clustering and curve/surface fitting. In the second stage, the mixing system is inverted, yielding the estimated sources. We use the SSCA approach for solving three types of mixtures: time/position varying instantaneous mixtures, single-path mixtures, and multipath mixtures. Real-life scenarios and simulated mixtures are used to demonstrate the performance of our approach.