NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.

Natural killer (NK) cells are innate lymphoid cells, and their presence within human tumors correlates with better prognosis. However, the mechanisms by which NK cells control tumors in vivo are unclear. Here, we used reflectance confocal microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ (IFN-γ) secretion from intratumoral NK cells. NKp46- and Ncr1-mediated IFN-γ production led to the increased expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors, which altered primary tumor architecture and resulted in decreased metastases formation. Injection of IFN-γ into tumor-bearing mice or transgenic overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis formation. Thus, we have defined a mechanism of NK cell-mediated control of metastases in vivo that may help develop NK cell-dependent cancer therapies.

Safety and Efficacy of a Thermomechanical Fractional Injury Device for Periorbital Rhytides.

BACKGROUND: Periorbital rejuvenation is a common cosmetic concern. A fractional thermomechanical skin rejuvenation system was developed to offer clinical improvements from direct heat transfer. OBJECTIVE: A prospective study evaluated the efficacy and safety of the device for periorbital fine lines and wrinkles. MATERIALS AND METHODS: Subjects with moderate-to-severe periorbital rhytides were enrolled and underwent 4 monthly treatments with a novel device using thermomechanical fractional injury (Tixel 2; Novoxel, Netanya, Israel). RESULTS: Fifty-one subjects were enrolled. Mean age was 56.8 years, and 88.2% were women. Fitzpatrick skin Types I to IV were included. For Fitzpatrick Wrinkle Classification System (FWCS), mean baseline score was 5.7. Per investigator, there was a mean 2.0-grade improvement in FWCS at 3-month follow-up ( p < .0001). Per 3 blinded physician raters, there was a mean improvement of 2.2 ( p < .0001), 2.0 ( p < .0001), and 1.2 ( p < .0001) in FWCS at 3-month follow-up. Each of the raters correctly identified posttreatment images for 87.5%, 77.1%, and 75.0% of subjects. At least 2 raters agreed on grading 83.3% of subjects as responders. There were no severe adverse events. Subjects experienced minimal pain and downtime. CONCLUSION: A novel device using thermomechanical fractional injury was demonstrated to be safe and effective in the treatment of periorbital rhytides.

CO2 Laser Matricectomy for the Treatment of Pincer Nail Deformity: A Retrospective Cohort Study.

BACKGROUND: Pincer nail deformity (PND) is a common toenail disorder characterized by transverse over-curvature of the nail plate. It can cause severe pain, chronic inflammation, and recurrent infections. Both conservative and surgical treatment options carry different disadvantages of limited efficacy, high recurrence rate, and poor cosmetic outcome. The study aimed to evaluate the safety and effectiveness of carbon dioxide (CO2) laser matricectomy for the treatment of PND. METHODS: The database of the laser unit of a tertiary medical center was retrospectively searched for all patients who were diagnosed with PND in 2016-2022 and treated with lateral and/or medial matricectomy using CO2 laser. Clinical and follow-up data were collected from the medical files.  Results: The cohort included 19 patients (5 male, 14 female) who underwent 25 partial matricectomies during the study period (some patients had more than one diseased nail). All procedures were successful, with no intraoperative or postoperative complications. There was one documented recurrence at 7 months after treatment. CONCLUSION: Partial CO2 laser matricectomy is safe and effective for the treatment of PND. J Drugs Dermatol. 2023;22(11):1099-1102     doi:10.36849/JDD.7574.

Laser and light therapy for pediatric hair removal: a systematic review.

Hair removal with lasers and intense pulsed light (IPL) is considered safe. However, data on the efficacy and safety of these procedures specifically in the pediatric population remain sparse. To determine the efficacy and safety of lasers and IPL for hair reduction in children and adolescents, a systematic review was conducted of original studies evaluating hair removal with lasers or IPL in patients aged less than 18 years. Primary outcome measures were efficacy and safety of treatment. The literature review yielded 2 retrospective cohort studies and 11 case reports/case series including a total of 71 patients aged 9 months to 17 years. Diagnoses ranged from localized lumbosacral to generalized hypertrichosis. Six treatment modalities were evaluated: alexandrite, Nd:YAG, Q-switched Nd:YAG, ruby, and diode lasers and IPL. Only one of the cohort studies (n = 28), using the ruby laser, provided efficacy data. The results showed a 63% hair loss in 89% of patients after completion of treatment, although partial regrowth was evident during 6 to 32 weeks of follow-up. Most of the case reports and case series (10/11) reported significant hair reduction following laser and IPL treatments. None of the patients experienced scarring or dyspigmentation. Some kind of pain management was necessary in 65% of patients; 25% required general anesthesia. On the basis of the limited available data which consisted primary of case reports and case series, lasers and IPL might be effective for pediatric hair reduction. Recurrence following treatment may be higher in children than adults, and pain control may be a limiting factor.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg 0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Treating pediatric cutaneous Leishmania tropica with systemic liposomal amphotericin B: A retrospective, single-center study.

Leishmania tropica (L. tropica) cutaneous leishmaniasis (CL) is associated with high morbidity and low response rate to therapy, especially in pediatric patients. Intravenous (IV) liposomal amphotericin B (LAmB) has been used off-label as a treatment for L. tropica CL for many years. However, data regarding its efficacy and safety in children is lacking. In order to evaluate the efficacy and safety of IV LAmB for treating pediatric patients with L. tropica, we retrospectively reviewed electronic medical records of 24 children who were diagnosed with L. tropica CL and treated with IV LAmB during 2014-2020, at a tertiary medical center in Israel. Fourteen (58%) completed the treatment protocol and 10 (42%) experienced an infusion-related adverse event (IRAE) leading to treatment termination. Complete response was noted in 6/14 (43%) patients, while 8/14 (57%) failed to respond. Lower response rate was noted in lesions involving the mid-facial area. The relatively low response rate is speculated to result from a low dose of LAmB, short follow-up period, and difficult to treat anatomic locations. The observation of a lower response rate for mid-facial lesions should be validated in larger cohorts. The highrisk of IRAE should be considered in physician decisions regarding this treatment.

Occupational Chronic Contact Dermatitis Successfully Treated with Dupilumab: A Case Series.

BACKGROUND: Occupational contact dermatitis may progress to a chronic course with an unfavorable prognosis. Dupilumab has been shown to be effective as a treatment for moderate-to-severe atopic dermatitis as well as other types of dermatitis. OBJECTIVES: The aim of the study was to describe cases of chronic recalcitrant occupational contact dermatitis treated with dupilumab and with long-term follow-up. METHODS: A retrospective review of 6 patients treated with dupilumab for chronic occupational contact dermatitis for periods of up to 30 months was performed. RESULTS: All 6 patients had a positive and sustainable response, with dermatitis clearance and the ability to sustain work tasks. CONCLUSIONS: We report a case series of atopic and nonatopic workers with occupational chronic contact dermatitis who failed to achieve remission under various systemic modalities but did so using dupilumab. We suggest considering dupilumab treatment for recalcitrant occupational contact dermatitis.

The Bacteriology of Skin Lesions in Patients with Hidradenitis Suppurativa Is Associated with Previous Antibiotic Treatment in the Community Setting: A Referral Center Experience.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by inflammatory nodules and abscesses. The pathogenic role of bacteria is not fully understood. As the diagnosis is usually delayed, patients are often treated with several lines of antibiotics in a nonstandardized fashion. The aim of the study was to investigate and compare the bacteriology of active HS lesions in patients treated or not treated with antibiotics in the community setting before referral to a dedicated HS clinic. METHODS: Purulent skin lesions of patients with HS referred to the HS Clinic of Rabin Medical Center in 2009-2020 were cultured. Data were collected from the patients' medical files and microbiology reports. The correlation between the location of the skin lesion and the bacteriologic profile was analyzed, and the effects of previous antibiotic treatment on the bacteriologic profile of the lesions and susceptibility patterns of the cultured bacteria were evaluated. RESULTS: Pus (or tissue) from inflammatory lesions of 97 patients with HS was cultured. Mean (SD) patient age was 39.5 (13.0) years, and mean delay in diagnosis was 7.3 (8.3) years. Most patients (57.7%) had dominant involvement of one location, with the most active lesions concentrated in the genitalia, gluteal/perineal area, and axilla. Enterobacterales species were the most frequent isolates detected in all locations except the face and scalp. Seventy-eight patients (80.4%) had been treated in the community setting prior to referral with a median (range) of 2 (1-8) lines of antibiotics. The most commonly prescribed antibiotics were amoxicillin/clavulanate (22.0%), doxycycline/minocycline (16.8%), clindamycin (16.2%; monotherapy 8.1%, clindamycin with rifampicin 8.1%), and cephalexin (13.9%). Compared to the previously untreated patients, cultures of lesions from the previously treated patients yielded a higher percentage of gram-negative Enterobacterales (the most common isolates in this group) (31.3% vs. 10.3%) and a significantly higher median number of isolates per culture (2 vs. 1, p < 0.0001). Gram-positive bacteria, usually considered contaminants (mainly coagulase-negative staphylococci) accounted for 31.0% of the isolates in the previously treated group. Susceptibility testing for the entire cohort revealed 100% bacterial sensitivity to ciprofloxacin. Staphylococcus spp. were 100% sensitive to rifampicin. Both gram-positive and gram-negative bacteria had high sensitivity to trimethoprim and sulfamethoxazole. CONCLUSION: Nonstandardized antibiotic treatment of HS in the community setting can skew the microbiology of skin lesions toward gram-negative bacteria. Therefore, treatment with trimethoprim and sulfamethoxazole or ciprofloxacin, either alone or combined with rifampicin, may be considered.

Bullous Pemphigoid and Scabies: Is There an Association?

BACKGROUND: Bullous Pemphigoid (BP) is an autoimmune subepithelial bullous disease. Several reports suggested an association between BP and scabies. OBJECTIVE: We aimed to evaluate whether an association between BP and scabies exists. METHODS: This is a retrospective matched case-control study. We retrospectively identified BP patients treated in our clinic between January 1, 2009, and December 31, 2016. Each patient was assigned to 3 control subjects (matched by age and sex) treated in our clinic, not due to BP. The study group was examined for a scabies diagnosis within the 3 years prior to BP diagnosis; the control group was examined for a scabies diagnosis 3 years prior to its first visit in our clinic. RESULTS: Fifteen out of the 87 (17.2%) BP patients were diagnosed with scabies within the 3 years prior to their initial BP diagnosis, compared to only 4.2% (11 out of 261) among the control group. The odds ratio of scabies history was 4 times higher among BP patients compared to the control group (OR=4.23; 95% CI: 1.50–11.91, P=0.007). LIMITATIONS: A retrospective study design. CONCLUSIONS: An association between scabies diagnosis and BP is demonstrated in our study. J Drugs Dermatol. 2022;21(9):1009-1011. doi:10.36849/JDD.4900.

Clinical and histological evaluation of a dual sequential application of fractional 10,600 nm and 1570 nm lasers, compared to single applications in a porcine model.

The sequential application of fractional ablative/10,600 nm/CO2 followed by 1570 nm non-ablative laser treatment might produce better results than applying either laser treatment alone. However, histological data regarding the safety of this combination is lacking. This study aimed to assess and compare clinical effects, histological tissue damage, and wound healing after monochromatic and sequential fractional laser treatments. In this prospective porcine model study, three adult female pigs were each irradiated using three different wavelengths: (a) monochromatic fractional ablative CO2 laser; (b) monochromatic fractional non-ablative 1570 nm laser; (c) sequential fractional 10,600 nm/CO2 followed by 1570 nm laser treatment. There were six power levels in the monochromatic 1570 nm laser, five in the 10,600 nm/CO2, and five in the sequential treatment. The immediate skin reaction (ISR), crusting and adverse effects, was evaluated across different time points throughout the healing process. Wound biopsies were taken at immediately after (0) and at 3, 7, and 14 days after irradiation. Depth and width of craters, and width of coagulation zone were measured and compared. Similar ISR and crusting score values were obtained following the monochromatic and sequential irradiation in a similar dose-response manner. During 14 days of follow-up, the skin looked intact and non-infected with no signs of necrosis. The mean depth and width of craters were comparable only at the maximal energy level (240 mJ) of CO2 laser, with the coagulation size greater after the sequential treatment. In histology, a similar wound healing was evident. On day 3, crusts were observed above all lesions as was epithelial regeneration. The sequential irradiation with 10,600 nm/CO2 and 1570 nm lasers did not pose any additional risk compared to the risk of each laser alone.

Efficacy and safety of a thermal fractional skin rejuvenation system (Tixel) for the treatment of facial and/or scalp actinic keratoses.

Actinic keratoses are common cutaneous lesions with a potential to progress to invasive squamous cell carcinoma. Therefore, treatment is crucial. The Tixel® is a noninvasive thermomechanical device designed to transfer heat to the upper dermis in a controlled manner according to a predetermined setting. This study aimed to evaluate the safety and efficacy of a thermomechanical fractional skin resurfacing technology for the treatment of facial and scalp actinic keratoses. A prospective, open-label, before-after study was conducted in a tertiary medical centre from May 2020 to April 2021. Patients presenting with facial/scalp actinic keratoses of mild-to-moderate thickness underwent 2 or 3 Tixel treatments (depending on clinical improvement), 3-4 weeks apart. The reduction in lesion count and overall improvement in appearance were assessed by clinical examination and digital photography. Findings were compared between baseline and follow-up at 3 months after the last treatment session. Patient satisfaction was evaluated by questionnaire, and adverse effects were documented. A total of 20 patients participated in the study. All completed 2-3 treatments and follow-up visits. Assessment of digital photographs was performed by 2 assessors blinded to the timepoint at which each photo was taken (before or after treatment). The average number of lesions at baseline was 9.8 (± 4.8) and the mean reduction in lesion count was 7.9 (± 4.4) (80.6%). Complete clearance was observed in 31.6% of patients. No adverse effects were noted during treatment and follow-up. Most patients reported being "very satisfied" or "satisfied" with the treatment results (85%) and experience (95%). Treating facial and scalp actinic keratoses with the Tixel device was found to be effective and safe.

The relationship between atopy and allergic contact dermatitis in Israeli patients.

Introduction: Whether individuals with atopic diseases have a different risk of contact allergy compared to those who are non-atopic is controversial and data are conflicting. Aim: To explore the association between atopy and allergic contact dermatitis (ACD). Material and methods: This retrospective cross-sectional study included 301 patients referred to a tertiary clinic to evaluate ACD. Demographic details including personal and familial mucosal or cutaneous atopic status were recorded. Patch tests were tailored to their clinical presentations and relevant exposures. Results: At least 1 positive patch test reaction was observed in 177 patients (59% of the study cohort), of which 52% had a history of atopic diseases, compared with 44% of patients with a negative patch test result (p = 0.2). Additionally, 147 patients had an atopic background, of which 92 (62%) had ≥ 1 positive patch test result, compared with 55% of non-atopic patients (p = 0.2). Nickel sulphate was the most common contact allergen (13.4% of the patch test reactions). Conclusions: We identified a positive tendency for atopic diseases among individuals with ACD and vice versa. Our study supports the aggregate data from previous studies despite the non-significant differences between the study and control groups. However, further research performed in larger populations of patients is necessary to evaluate the real association between atopy and ACD on a solid basis. Our results indicate the necessity of systematic patch testing in patient setups with atopic background and chronic dermatitis.

Topical and systemic retinoids for the treatment of cutaneous viral warts: A systematic review and meta-analysis.

Cutaneous viral warts (CVW), caused by human papillomavirus, often have a self-limited course. However, some patients experience a recalcitrant disease despite treatment. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for viral warts are limited. To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of CVW. A systematic review and meta-analysis of topical or systemic retinoid treatment for CVW was performed in accordance with the PRISMA statement. The primary outcome was clinical response; secondary outcomes were recurrence rate and adverse events. Fourteen publications including 399 patients treated exclusively with retinoids (65% topical, 35% systemic) were evaluated. The complete response rate was 64% (95% CI, 46-78%; I2 =80%) for topical treatment and 61% (95% CI, 44-76%; I2 =69%) for systemic treatment. The most common side effects were irritant contact dermatitis and cheilitis, respectively. Relapse rates were 6% and 17%, respectively. The reviewed studies were considerably heterogenous and most lacked a control group. Both topical and systemic retinoids are effective and safe as monotherapy for CVW. Further studies are required to determine their exact role in this setting.

Treatment of Pemphigus with Rituximab: Real-Life Experience in a Cohort of 117 Patients in Israel.

BACKGROUND: A combined regimen of rituximab with corticosteroids for the treatment of pemphigus was effective in a prospective randomized controlled trial. OBJECTIVE: To assess real-life response to rituximab in patients with pemphigus. METHODS: A retrospective cohort of patients with pemphigus treated with ≥1 rituximab cycles (1,000 mg on days 0 and 14). The primary outcome was remission rate after 1 cycle. For efficacy analyses, a minimal 6-month follow-up was required. Adverse events were assessed in all patients. RESULTS: The cohort included 117 patients for safety analysis, 108 for efficacy analysis (median follow-up of 33 months). All but one received concomitant corticosteroids, a third also received adjuvants. Overall, 80/108 patients (74%) achieved remission after the first rituximab cycle at a median of 5.5 months. Relapses occurred in 39 patients (49%) at a median of 18 months. Repeating treatment in relapsed patients increased remission rates to 75 and 88% after the second and third cycles, respectively. Adverse events were similar to those of previous publications. Two elderly patients died of infections attributable to rituximab combined with high-dose corticosteroids. CONCLUSION: In a large real-life long-term cohort, rituximab with corticosteroids ± adjuvants induced remission in most patients with pemphigus, with relatively favorable safety. Repeating treatment following relapse or remission failure was beneficial.

Treatment of Pemphigus Vulgaris and Foliaceus with Adjuvant Rituximab Compared to Immunosuppression Alone: Real-Life Experience.

INTRODUCTION: In a randomized prospective trial, adjuvant rituximab was more efficacious than corticosteroids alone in the treatment of pemphigus; however, real-life data are limited. Rituximab treatment for pemphigus has only recently been introduced to the Israeli health basket. Previously, patients received rituximab if they paid out of pocket or through private insurance, separating patients into 2 treatment groups, mostly based on economic capability. METHODS: A retrospective cohort study of the 12-month clinical response of pemphigus vulgaris/foliaceus patients. We compared patients after a single cycle (1,000 mg on days 0 and 15 or weekly 375 mg/m2 for 4 weeks) of adjuvant rituximab with systemic corticosteroids ± steroid-sparing agents, to patients who were prescribed rituximab, could not obtain it, and received systemic corticosteroids ± steroid-sparing agents. RESULTS: Forty-five patients were included (adjuvant rituximab, n = 29; immunosuppression alone, n = 16). At baseline, rituximab patients had a higher mean pemphigus disease area index (PDAI) (p = 0.07) and higher mean daily dosages of prednisone (1.51 vs. 1.16 mg/kg, p = 0.39). All patients but 1 in the rituximab group continued systemic steroids, and 31% in the rituximab group versus 50% in the immunosuppression-alone group received systemic adjuvants. At 12 months, partial or complete remission rates (on or off maximum 40 mg/day prednisone equivalent) were nonsignificantly higher in the rituximab group (62 vs. 50%, p = 0.53); however, patients on rituximab showed faster remissions (3.4 ± 1.9 vs. 5.9 ± 3.6 months; p = 0.03) with a trend for a greater PDAI reduction (p = 0.051). Adverse events were comparable. CONCLUSIONS: In this real-life study, a single cycle of rituximab achieved more remissions and sooner compared to conventional immunosuppression, but the differences were not significant, probably due to a small sample size and severe baseline disease in the rituximab group. Future real-life studies on larger groups are needed.

Topical and Systemic Retinoids for the Treatment of Genital Warts: A Systematic Review and Meta-Analysis.

BACKGROUND: Genital warts, caused by the human papillomavirus, are a common sexually transmitted disease. The warts can regress spontaneously or exhibit a persistent clinical course. Various therapeutic modalities are available, yet none is curative, and there may be recurrences. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for genital warts are limited. OBJECTIVE: To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of genital warts. METHODS: A systematic review and meta-analysis of all publications evaluating topical or systemic retinoids for the treatment of genital warts was performed. The primary outcome was complete response (CR); the secondary outcomes were recurrence rate and adverse events. RESULTS: Six publications were evaluated, three randomized controlled trials and three prospective cohort studies, including a total of 141 patients with genital warts treated exclusively with retinoids (90% with isotretinoin). CR rates were 100% for systemic etretinate (3 out of 3 patients, 95% CI 28-81%) and 56% for isotretinoin (95% CI 28-81%; I2 = 84%). Topical etretinate did not induce CR. The most common side effect of topical agents was irritant contact dermatitis (36%) and that of systemic agents mucocutaneous disorders (80%). The relapse rate was 12% for oral isotretinoin and was unavailable for the other modalities. CONCLUSIONS: Current data suggest that unlike topical retinoids, systemic retinoids are an effective and safe treatment for genital warts. Further studies are required to determine their specific role and the most effective regimen for each derivative.

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.

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.

Isolated solar angioedema: A systematic review of the literature.

Solar urticaria is a well-recognized photodermatosis, sometimes accompanied by angioedema. However, isolated solar angioedema (ISA) is a rare and unrecognized entity. The purpose of our work was to systematically review the available data on ISA. Therefore, a systematic review of studies evaluating ISA was performed. Additionally, a case of a 21-years-old patient from our photodermatosis service is presented. The search yielded 421 publications, with 3 eligible for review. Together with our case, 5 cases were included overall. All patients were female. Four out of 5 patients first experienced ISA at childhood or early adulthood (age range 6-22 years). UVA photoprovocation was positive in the 3 out of the 4 patients who were tested. Improvement was noted following NB-UVB hardening (2 out of 5 patients) or a short course of oral prednisone (3 out of 5 patients) combined with regular sunscreen application. To conclude, ISA is an extremely rare entity, although it may be underdiagnosed due to lack of awareness. The clinician must consider ISA in the differential diagnosis of angioedema since it can have a detrimental effect on quality of life. Besides sun avoidance, there is no consensus regarding treatment.