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.
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).To evaluate the characteristics of inherited genetic late-onset (IGLO) EPP.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.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.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.
<b><i>Introduction:</i></b> Surgery is commonly regarded as the mainstay of treatment of extramammary Paget disease (EMPD)<b><i>;</i></b> however, nonsurgical approaches have gained popularity in recent years. <b><i>Objectives:</i></b> To review the published evidence for the efficacy and safety of nonsurgical modes of therapy for EMPD. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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%; <i>I</i><sup>2</sup> = 37%) and had a satisfactory safety profile. In 14 heterogeneous studies (122 patients) evaluating photodynamic therapy (PDT), only 36% (95% CI, 22–53%; <i>I</i><sup>2</sup> = 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. <b><i>Conclusions:</i></b> 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.
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.To describe the cutaneous features of GCP in Israel.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.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.This study sheds light on the cutaneous features of the GCP, which have a substantial effect on patients' quality of life.
Abstract Background From a dermatologist's perspective, there are four major types of cutaneous porphyrias ( CP s): porphyria cutanea tarda ( PCT ), erythropoietic protoporphyria ( EPP ), variegate porphyria ( VP ) and hereditary coproporphyria ( HCP ). Scarce data are available regarding the epidemiology of CP s. Objectives To describe the epidemiology of CP s in Israel, including distribution, incidence and prevalence rates of major types. Methods This retrospective study includes all patients who were diagnosed with CP s between the years 1988–2018. It is based on data from Israel's National Service for the Biochemical Diagnoses of Porphyrias, and Israeli patients’ nationwide electronic medical charts. Incidence and prevalence rates were calculated. Results Of 173 patients with CP s diagnosed during a 30‐year period, 65 (38%) had VP , 62 (36%) had PCT , 31 (18%) had HCP and 15 (9%) had EPP ; with incidence rates of 0.29, 0.30, 0.17, 0.07, and prevalence rates of 6.3, 4.8, 2.9, 1.6, respectively, per million population. Characteristics of patients with PCT differed from those with other CP s with regard to lack of family history, older mean age at diagnosis [51 vs. 36 ( VP ), 35 ( HCP ) and 25 ( EPP ) years] and male predominance (81% vs. similar distribution). All patients with PCT were diagnosed at adulthood, while 20%, 19% and 15% of patients with VP , HCP and EPP , respectively, were diagnosed during childhood or adolescence. Conclusions Variegate porphyria and PCT were found to be the most prevalent in Israel; however, CP s might be underdiagnosed, thus dermatologists’ awareness of these rare disorders is highly important.
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.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.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.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.
Abstract 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.
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.
