Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

Kaposi varicelliform eruption: an unusual presentation caused by varicella zoster virus in a healthy adult patient - a case report.

BACKGROUND: Kaposi Varicelliform Eruptions (KVE), also known as eczema herpeticum, is a rare and potentially life-threatening dermatological condition primarily attributed to herpes simplex virus (HSV) infection, with less frequent involvement of Coxsackie A16, vaccinia, Varicella Zoster, and smallpox viruses. Typically associated with pre-existing skin diseases, especially atopic dermatitis, KVE predominantly affects children but can manifest in healthy adults. Characterized by painful clusters of vesicles and sores on the skin and mucous membranes, it often masquerades as other dermatological disorders. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief and inflammation, though their potential role as KVE triggers remains uncertain. CASE REPORT: Here, we present a case of an 18-year-old female with KVE attributed to Varicella Zoster virus (VZV) and successfully treated with oral acyclovir within a week, underscoring the significance of early recognition and intervention. KVE can manifest with systemic symptoms like fever, fatigue, and lymphadenopathy and may involve multiple organ systems, necessitating possible antibiotic use for complications. CONCLUSION: This case underscores the importance of prompt KVE identification and consideration of antiviral therapy to enhance patient outcomes. Further research is warranted to elucidate predisposing factors for this rare condition.

A triple combination of latanoprost, fractional CO2 laser, and platelet-rich plasma in localized vitiligo: A clinical and histopathologic study.

BACKGROUND: Several treatment modalities are available for the treatment of vitiligo due to the lack of a uniformly effective therapy. Topical latanoprost 0.005% is an effective topical treatment. Fractional CO2 laser alone or combined with platelet-rich plasma (PRP) has been proposed as effective adjunctive therapies. OBJECTIVES: We aimed to compare the efficacy of topical latanoprost 0.005% (Ioprost®, Orchidia, Egypt) combined with either add-on fractional CO2 laser or fractional CO2 -PRP versus topical latanoprost monotherapy in the treatment of localized stable vitiligo. PATIENTS/METHODS: The study included 60 patients randomly assigned into three equal groups. Group A patients received topical latanoprost drops only. Group B patients received topical latanoprost drops and fractional CO2 laser sessions at 2-week interval for 3 months. Group C patients received topical latanoprost drops and fractional CO2 laser sessions combined with PRP at a 2-week interval for 3 months. The mean improvement score by the physician was calculated 4 months after the start of the study. Punch skin biopsies were obtained before treatment and 4 months from the beginning of the study and stained with H&E and HMB-45 antibody for evaluation of pigmentation. RESULTS: Significant clinical improvement of vitiligo lesions with significant increase of re-pigmentation were reported in the three treated groups. Latanoprost in combination with fractional CO2 and PRP was associated with more significant therapeutic outcomes than either combined latanoprost and fractional CO2 or latanoprost alone. CONCLUSION: Fractional CO2 laser-PRP enhances the therapeutic efficacy of latanoprost 0.005% in the treatment of localized stable vitiligo.

Topical calcipotriol combined with urea 20% versus intralesional injection of triamcinolone acetonide, 5-fluorouracil, and methotrexate in the treatment of nail psoriasis: A comparative study.

There is no consistently effective treatment for psoriatic nails. Topical and intralesional modalities have been recently investigated and showed promising efficacy and safety. To compare the efficacy and safety of intralesional injection of 5-fluorouracil (5-FU), methotrexate (MTX), triamcinolone acetonide (TA) versus topical calcipotriol plus urea 20% in the treatment of nail psoriasis. This study included 60 patients with nail psoriasis who were randomly assigned to 4 groups, each containing 15 patients. The first 3 groups received intralesional injection of 0.1 ml of 5-FU (group A), MTX (group B), and TA (group C) into the nail matrix and bed monthly for 3 months. Group D received a topical combination of calcipotriol/urea 20% twice daily for 3 months. Therapeutic response was assessed every month for 3 months using the target nail psoriasis severity index (NAPSI). The mean percentage of improvement was significantly higher in topical calcipotriol/urea combination (57.1 ± 26.4) than intralesional TA (44.2 ± 32.7), intralesional MTX (37.7 ± 14.2), and intralesional 5-FU (29.6 ± 14). Adverse effects were mild and insignificant in the studied groups. Topical calcipotriol/urea combination seems to be more effective and safe than intralesional injections of 5-FU, MTX, and TA.

Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction.

The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.

The effect of continuous high versus low dose oral isotretinoin regimens on dermcidin expression in patients with moderate to severe acne vulgaris.

The continuous low dose (LD) isotretinoin is frequently used in the treatment regimen for acne vulgaris. However, data about its antimicrobial are lacking. The present study aimed to investigate dermcidin expression and the effects of low and conventional dose isotretinoin on its expression in acne vulgaris patients. Skin dermcidin expression was investigated in 30 patients with moderate-severe acne vulgaris and 15 healthy control subjects using ELISA. 15 patients were given continuous low-dose isotretinoin (20 mg/day) and the other 15 given the conventional high dose (0.5 mg/kg/day). Skin biopsies were taken at the start of the study and 6 months later. Dermcidin was significantly lower in acne vulgaris patients (p < .001). Both isotretinoin regimens significantly raised dermcidin levels compared to pre-treatment values (p < .001). Relapse after 12 months was not statistically different among the two isotretinoin regimens (p = .464). Pretreatment global acne grading system score of 28.6 ± 6.4 was reduced to 6 ± 6.1 following isotretinoin treatment (p < .001). Relapse was significantly related to posttreatment dermcidin levels (p = .017). Dermcidin expression is reduced in acne vulgaris. Conventional and LD isotretinoin regimens are associated with increased dermcidin expression.

Zinc alleviates high fat diet-induced spermatogenic dysfunction in Wistar rats: role of oxidative stress, HMGB1 and inflammasome.

Whether chronic inflammation in the genital tract induced by obesity shares in spermatogenic dysfunction is not clearly known. We aimed to study the effect of high fat diet (HFD) on spermatogenesis, seminal oxidative stress (malondialdehyde (MDA)) and inflammatory markers (high mobility group box 1 (HMGB1), nucleotide-binding oligomerization domain, leucine rich repeat and pyrin-3 domain containing (NLRP3)) in the rat testes and the role of zinc on testicular dysfunction and chronic inflammation in high fat diet (HFD) fed rat testes. This parallel group comparative experimental study included 36 male wistar rats divided into 3 groups: group A (fed on normal control diet); group B (fed on high fat diet (HFD) only); and group C (fed on HFD with zinc supplementation 3.2 mg/kg/day orally). At the end of the 12th week, sperm count, viability and motility were assessed by computer-assisted seemen analysis (CASA), seminal malondialdehyde measured by calorimetry and histopathological examination of testicular sections was done. Immunohistochemical staining was done for HMGB1 and NLRP3 evaluation. Sperm count was lowest in group B. Groups A and C showed statistically significant higher mean sperm vitality, total and progressive motility scores (p < 0.001), while no difference was found between the groups A and C (p > 0.05). Seminal malondialdehyde level was significantly highest in group B. Tubular diameter, epithelial height and Johnsen score were significantly lowest in group B. Significantly higher HMGB1 and NLRP3 levels were demonstrated in group B (p < 0.001). Obesity is associated with testicular dysfunction, testicular oxidative stress and increased testicular HMGB1 and NLRP3. We suggest a beneficial effect of zinc on testicular function in HFD-rats.

Fractional CO2 laser - assisted methylene blue photodynamic therapy is a potential alternative therapy for onychomycosis in the era of antifungal resistance.

BACKGROUND: Treatment of onychomycosis is challenging by virtue of the impact of nail disfigurement, the location of the fungi within the nail and reported antifungal resistance worldwide. Light-based technologies are promising primary or adjunctive therapeutic modalities. We aimed to compare the efficacy of photodynamic therapy and fractional CO2 laser monotherapy either alone or in combination for onychomycosis. PATIENTS AND METHODS: This prospective randomized comparative study was conducted on 51 onychomycosis patients divided into three groups. In group A, patients were treated using 6 photodynamic therapy sessions using methylene blue and IPL (560 to 700 nm, fluence 12 J/cm2). Group B patients were treated using 6 bimonthly fractional CO2 laser sessions (10,600 nm, 1.600 mj energy and 0.6 mm density) and group C patients were treated using 6 combined fractional CO2 laser and photodynamic therapy sessions. Patients were evaluated mycologically, dermoscopically and clinically by calculation of proximal nail diameter percentage at baseline, monthly, at the end of treatment and after a 6-month follow-up period post-treatment. RESULTS: Candida was the most commonly isolated organismin in 64.7%, 70.6% and 70.6% of the pateints in groups A, B and C, respectively. The dermoscopic findings in the total dystrophic onychomycosis was subungual hyperkeratosis in 6 patients (100%), longitudinal streaks and striae in 1 patient (16.7%). In dorsolateral subungual onychomycosis, jagged proximal edge in 31 patients (70.5%), and pigmentation in 30 patients (68.2%) were noted. In proximal subungual onychomycosis irregular matt patches were seen in 1 patient (100%). Proximal nail diameter percentage showed statistically significant improvement after treatment and 6 months follow up in the 3 studied groups. Mean increase of proximal nail diameter after treatment was highest in group C (52.94 ± 20.24), followed by group B (43.82 ± 21.03) and least in group A (35.29 ± 17.0). This difference was statistically significant (p = 0.044). Reported side effects were mild-moderate pain, discoloration and paronychia. CONCLUSION: We conclude that fractional CO2 laser and photodynamic monotherapy, and their combination achieve high success rates, good patient satisfaction and safety profile. Fractional CO2-assisted photodynamic therapy is associated with the highest improvement over either fractional CO2 or photodynamic therapy alone.

Impact of sofosbuvir/ledipasvir versus sofosbuvir/daclatasvir regimens on the male sexual function of patients with chronic hepatitis C.

Direct-acting antivirals (DAAs) are associated with remarkable efficiency and safety profiles; however, their effect on erectile function remains insufficiently studied. This study included 200 male patients with chronic hepatitis C virus (HCV) infection divided into groups A and B and 100 healthy controls. Group A received sofosbuvir (SOF) 400 mg/ledipasvir 90 mg (Harvoni), whereas group B received SOF 400 mg/ daclatasvir 60 mg for 3 months. The Arabic version of the five-item International Index of Erectile Function-5 (IIEF-5) questionnaire was used to assess erectile function before and after completion of therapy and 3 months after. Erectile dysfunction (ED) was present in 74.5% of the patients and 14% of the controls. Immediately after treatment, group B (22.5±2.6) had a significantly higher mean IIEF-5 score than did group A (17.3±3.3) (p<0.001). Three months after treatment, all groups had no significant differences in mean IIEF-5 scores (group A: 23.1±1.9, group B: 23.3±1.9, controls: 23.7±2.3); however, free testosterone (FT) levels were significantly higher compared with pre-treatment. Both treatment regimens were associated with the improvement of erectile function and sex hormonal milieu. SOF/daclatasvir was associated with earlier improvement of erectile function compared with SOF/ledipasvir.

Psychological and Sexual Health During the COVID-19 Pandemic in Egypt: Are Women Suffering More?

INTRODUCTION: Psychological consequences of the COVID-19 pandemic include pandemic triggered feelings of fear, uncertainty, and anxiety added to the effects of restricting the population's activities in lockdown. AIM: We aimed to study the effect of COVID-19 pandemic on sexual satisfaction of females and males in Egypt and to evaluate possible predictive factors. METHODS: Married men and females in Egypt were invited to respond to an online questionnaire. The questionnaire addressed medical history, socioeconomic status, sexual performance satisfaction before and during the lockdown in addition to validated Arabic questionnaires for depression, sexual function in males and females, and sexual satisfaction (Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Female Sexual Function Index, International Index of Erectile Function-5, Index of Sexual Satisfaction, respectively). MAIN OUTCOME MEASURE: The main outcome measures were frequency of depression, anxiety, sexual dysfunction, and sexual satisfaction in males and females during COVID-19 lockdown. RESULTS: A total of 479 females and 217 males completed the questionnaire. Sexual satisfaction was significantly higher before (91.2%, 73.5%) than during lockdown (70.5%, 56.2%) in both males and females, respectively. During lockdown, significantly more males (70.5%) reported being satisfied with their sexual performance than females (56.2%) (P < .001). More than half of the male subjects (68.2%) had no erectile dysfunction while 97.3% females scored ≤26.5 on the Female Sexual Function Index scale suggestive of sexual difficulties. Sexual stress was significantly greater in females (70.8%) than males (63.1%). Educational level, occupation, anxiety, and erectile dysfunction were independently associated with sexual stress in males. Being a housewife or unemployed, husband's age >35 years, marriage duration of 5-10 years, anxiety, and female sexual dysfunction were predictors of sexual relation stress in females. CONCLUSION: COVID-19 pandemic was associated with lower sexual satisfaction in both genders. Females however suffered more anxiety and depression and thereby greater risk of sexual function difficulties and sexual dissatisfaction. Intervention strategies in order to lessen the suffering of affected individuals particularly after the pandemic are recommended. Omar SS, Dawood W, Eid N, et al. Psychological and Sexual Health During the COVID-19 Pandemic in Egypt: Are Women Suffering More. Sex Med 2021;9:100295.

Clinical and dermoscopic evaluation of fractional carbon dioxide laser in management of keratosis pilaris in Egyptian type skin.

BACKGROUND: Numerous treatment modalities for keratosis pilaris have been tried with limited success. AIM: To determine the efficacy, safety, and tolerability of fractional CO2 laser in the treatment of KP. PATIENTS AND METHODS: This prospective, single-blinded split-body placebo-controlled comparative study was conducted on 60 patients with bilateral KP of arms (group A) and thighs (group B). One side randomly received fractional CO2 laser treatment (power 12 W, time on 3 ms, PPI 5) in the form of two sessions four weeks apart. The contralateral control side was treated with a topical keratolytic (10% urea). Standardized digital clinical and dermoscopic photographs were obtained at each visit. RESULTS: Significant improvement has been demonstrated clinically and dermoscopically in both arm and thigh lesions after fractional CO2 laser. In group A, excellent improvement was noted in 10 patients (33.3%), good improvement in 18 patients (60%), and moderate improvement in 2 patients (6.7%) at the second visit. In group B, minimal improvement was noted in 2 (6.7%) patients, moderate improvement in 16 patients (53.3%), and good improvement in 12 patients (40%) at the second. Control sides showed minimal improvement on the arm lesions only. No side effects were reported in both groups. The mean pain score in group A was not significantly different from that group B (P = .057). Patient satisfaction was significantly higher in the laser-treated side arm lesions (P < .001). CONCLUSION: Fractional CO2 laser was associated with significant clinical and dermoscopic improvement of keratosis pilaris lesions in Egyptian patients.

Prevalence of ocular findings in a sample of Egyptian patients with psoriasis.

BACKGROUND: Psoriasis is a common disorder worldwide. The prevalence of psoriasis in Egypt, an African country with a Caucasian population, ranges 0.19-3%. Despite this relatively high prevalence of psoriasis, there are no epidemiologic data regarding the burden of associated eye affection. Determining the magnitude of the problem could help in offering better integrated health services. AIM: The purpose of this study was to evaluate eye involvement in a sample of Egyptian psoriatic patients. PATIENTS AND METHODS: This case-control study included 100 patients with psoriasis and 100 age and sex matched healthy controls. Psoriasis extent and severity was graded by psoriasis area and severity index (PASI). Complete ophthalmological examination and tests for dry eye were performed to all subjects. RESULTS: The mean age of the psoriasis group was 50.7 ± 14.3 years. Thirty eight percent of the cases were females. The mean duration of psoriasis was 10.1 ± 7.5 years. Psoriasis patients had more conjunctival injection (n = 40, P = 0.035), more pinguecula (n = 38, P = 0.048) than controls. Ocular surface disease index (OSDI), tear breakup time (TBUT), Schirmer I, and Rose Bengal staining showed statistically significant positive results in the psoriasis group. CONCLUSION: This is the first report on the prevalence of eye comorbidities in Egyptian psoriatic patients. Dry eyes were more common with psoriasis, particularly the erythrodermic type. Other ocular findings were not statistically significantly different except for conjunctival injection and pinguecula.

Treatment of auricular keloids by triple combination therapy: Surgical excision, platelet-rich plasma, and cryosurgery.

BACKGROUND: Surgical excision alone for auricular keloids is frequently followed by recurrence making combining treatment options necessary. OBJECTIVE: We aimed to assess the long-term efficacy of combining surgical excision, cryosurgery, and platelet-rich plasma (PRP) in treatment of auricular keloids. METHODS: This interventional study was carried out on fifty auricular keloids in 50 patients. Patients were subjected to a combination therapy of surgical excision of the keloids, intraoperative cryosurgery, and PRP injections. The primary endpoint was defined as the number of patients who achieved major flattening of the keloid (reduction of more than 80% of the keloid) after a follow-up of 12 months. RESULTS: After follow-up of 12 months, 74% of the keloids achieved complete flattening in 10 cases and significant flattening in 14 cases. Thirty-four of the 50 keloids (68%) were treated with only excision, cryosurgery, and PRP and did not relapse. Three keloids (6%) had minor relapse after the first treatment but were considered persistent major flattening at the end of the study. Three other keloids (6%) needed intralesional triamcinolone to achieve major or complete flattening without further relapse. Treatment failure was observed in 30% who achieved <30% reduction in their surface. Treatment side effects were transient pain and focal hypoesthesia. CONCLUSIONS: This combination therapy was effective for treatment of auricular keloids, with a low recurrence rate and a favorable cosmetic outcome. Therapy was well tolerated and without significant side effects.