A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab - a new side effect after 15 years of usage.

BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis. CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists.

Styling without shedding: Novel topical formula reduces hair shedding by contracting the arrector pili muscle.

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α1 adrenergic receptor agonist, can be used to contract the arrector pili muscle of the follicular unit; thus, increasing the force required to pluck hair and reducing shedding during brushing. While demonstrating efficacy, phenylephrine has several drawbacks when applied to the scalp, including the possibility cardiovascular events. We hypothesized that a high concentration of a weak α1 agonist would allow for: (a) rapid penetration through the stratum corneum eliciting a quick response; (b) a low probability of cardiac adverse events owing to the low receptor binding affinity; and (c) an efficacy of the weak α1 agonist similar to that of phenylephrine at the local site of application. Accordingly, we developed a novel topical solution, AB-102, containing a high concentration of a weak α1 agonist. Several studies were conducted to test the safety and efficacy of AB-102. In a dose escalating safety study, utilizing a wearable holter monitor, we observed no cardiac or hemodynamic adverse events. In addition, in a controlled efficacy study, AB-102 reduced the number of hairs shed during brushing by up to 77% (average of 38%).

Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB.

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

Mixed vitiligo of Blaschko lines: a newly discovered presentation of vitiligo responsive to combination treatment.

Vitiligo, depigmenting disorder of the skin and mucous membranes, affects up to 1% of the population worldwide. It is classified into four major types: segmental, non-segmental, mixed, and unclassified type. Non-segmental vitiligo refers to non-dermatomal distribution of lesions, while dermatomal distribution of lesions is present in patients with segmental vitiligo. Segmental vitiligo can also follow Blaschko lines - pathways of epidermal cell migration and proliferation during the development of the fetus. Here, we present patient with segmental and non-segmental vitiligo following Blaschko lines with excellent therapeutic response to combined therapy. Prior to our report, a case of segmental and non-segmental vitiligo followed by Blaschko lines was never described, therefore we suggest the term "mixed vitiligo of Blaschko lines" to describe this entity. This is also a rare case in which 90% repigmentation was achieved in patient with segmental and nonsegmental vitiligo following Blaschko lines in only 2 months of combined therapy.

New anti-aging strategies: a narrative review.

The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and cardiovascular and neurodegenerative diseases. This review provides an overview of the latest advancements in this field, considering both pharmaceutical and non-pharmaceutical approaches. Electronic literature search involved three databases: MEDLINE, Cochrane, and Google Scholar, supplemented by other available literature. Strategies for delaying aging and related diseases comprise pharmaceutical interventions and lifestyle choices. It is crucial for these strategies to be substantiated by research-based evidence. Lifestyle options include fasting, fasting-mimicking, and ketogenic diets. Anti-aging drugs and supplements operate through diverse mechanisms. Calorie restriction mimetics include the activator of AMP-activated protein kinase (metformin) and inhibitor of mTOR (rapamycin), alongside rilmenidine, exhibiting both effects. Rosmarinic acid, a natural product, functions through its anti-glycation properties. Age-related protein crosslinks are acknowledged as a causative factor in age-related diseases. Anti-aging medicine is an evolving field with a multitude of drugs and strategies, necessitating further clinical studies and long-term follow-up based on clinical experience and insights gained from delayed adverse events.

Long-term clinical follow-up and molecular genetic findings in eight patients with triple A syndrome.

UNLABELLED: The triple A syndrome (Allgrove syndrome, OMIM #231550) is caused by autosomal recessively inherited mutations in the AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystemic disease is characterised by achalasia, alacrima, adrenal insufficiency and neurological impairment. We analyse long-term clinical follow-up and results of sequencing of the AAAS gene in eight patients with triple A syndrome aged from 2 to 35 years. At the time of diagnosis, all patients presented with alacrima, neurological dysfunction, dermatological abnormalities, seven of them with adrenal insufficiency and five of them with achalasia. Sequencing of the AAAS gene identified the p.S263P mutation in five of eight patients, supporting the hypothesis that this mutation is a founder mutation in Slavic population. One of the patients is homozygous for the p.S263P mutation, two are compound heterozygous for the p.S263P and the p.G14fs mutation, two are compound heterozygous for the p.S263Pro mutation and p.S296Y mutation, two are compound heterozygous for the p.G14fs and the p.Q387X mutations and one is homozygous for the p.Q387X mutation. In the course of the follow-up time of 4-29 years, progression of existing and appearance of new symptoms developed. Although severe, many of these symptoms presented in all six young adult patients are often overlooked or neglected: postural hypotension with blurred vision and syncope, hyposalivation resulting with complete edentulosis, talocrular contractures with permanent walking difficulties and erectile dysfunction in male patients. Triple A syndrome is a progressive debilitating disorder which may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment. CONCLUSION: Long-term follow-up of patients with triple A syndrome revealed a variety of the clinical features involving many systems. Progressive natural course of the disease may seriously affect quality of life and even be life-threatening in patients with severe neurological impairment.

Photodynamic therapy in dermatology: current treatments and implications.

This article provides an update on photodynamic therapy by discussing each of the essential components in sequence: mechanisms of action, common photosensitizers, typical light sources, and indications. In dermatology, photodynamic therapy (PDT) is mainly used in the treatment of superficial skin cancers: actinic keratoses, Bowen's disease and superficial basal cell carcinomas. However the range of indications has been expanding continuously. PDT is also used for the treatment of other oncological indications and non-malignant conditions such as acne vulgaris and photoaged skin. The 5-aminolevulinic acid (ALA) or its methyl ester (MAL) is applied topically as photosensitizer before activation with visible light. The advantages of topical PDT are: ability to treat multiple lesions simultaneously, low invasiveness, good tolerance and excellent cosmetic results.

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. AIMS: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. PATIENTS/METHODS: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days. RESULTS: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). CONCLUSIONS: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.

Two siblings with triple A syndrome and novel mutation presenting as hereditary polyneuropathy.

The clinical and molecular data on triple A syndrome in two siblings (girl 3.5 years and boy 5.5 years at presentation) with early onset of neurological dysfunction are described. Both patients showed delayed developmental milestones and neurological dysfunctions (motor and sensory demyelinating neuropathy, marked hyperreflexia, calves hypothrophy, pes cavus, gait disturbance) in early childhood, when erroneously diagnosed with hereditary polyneuropathy, most likely Charcot-Marie-Tooth disease. After a severe adrenal crisis in the younger sister at the age of 3 years, the older brother aged 5.5 years was also evaluated and latent adrenal insufficiency was discovered. As both of the siblings had alacrima, hyperkeratosis of palms, cutis anserina, and nasal speech, diagnosis of triple A syndrome was considered. Sequencing of the AAAS gene detected a compound heterozygous mutation consisting of a novel mutation p.Ser296Tyr (c.887C>A) in exon 9 and a previously described p.Ser263Pro (c.787T>C) missense mutation in exon 8 in both siblings. In conclusion, triple A syndrome should be considered in patients presenting with early neurological dysfunction and developmental delay. Alacrima as the earliest and most consistent clinical sign should be investigated by Schirmer test. Patients should be regularly tested for adrenal dysfunction to prevent life-threatening adrenal crises.

Unusual presentations of actinomycosis: a case series and literature review.

INTRODUCTION: To review unusual actinomycosis cases that appeared as a diagnostic and therapeutic challenge at our institution and to present a literature review on the usual clinical presentations. METHODOLOGY: This retrospective review included all patients hospitalized for actinomycosis in a 10-year period at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. RESULTS: A total of 15 patients were hospitalized during the observed period, 9 (60%) females and 6 (40%) males. The localizations of actinomycosis were: pelvis (5), lungs (3), blood stream (2), colon (1), penis (1), stomach (1), skin (1), cervicofacial region (1). We present four unusual cases: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft. CONCLUSIONS: Actinomycosis was a very rare clinical problem in our clinical practice (0.032% of all hospitalizations and 0.0034% of all outpatients) but among those cases classical clinical presentations were also very rare.

Novel yeast extract is superior to colloidal oatmeal in providing rapid itch relief.

BACKGROUND: Approximately, 13.5% of the population suffers from chronic itch. Many cosmetic and pharmaceutical treatments for itch are available; however, cosmetic treatments are not reliably effective and most pharmaceutical formulations carry the risk of adverse events with chronic use. AIMS: Previously, we have reported a novel extraction process of Saccharomyces cerevisiae, that is, Baker's yeast. The extract obtained from the novel process demonstrates superior anti-itch properties compared to other yeast extracts. In our previous study, we demonstrated that, after 30 minutes, the extract significantly reduced itch when compared to a placebo lotion (P = .002). METHODS: In the present study we conducted a head-to-head comparison with the leading cosmetic itch product: lotion containing colloidal oatmeal (CO). A randomized double-blinded study of 60 patients was conducted. RESULTS: In our study, the novel yeast extract was vastly superior to the CO containing lotion (Aveeno™ Eczema Therapy Moisturizing Cream). We saw statistically significant difference in the reduction of itch (P = .0001) using the novel yeast extract vs the CO lotion. Additionally, the yeast extract was shown to relieve itch in as little as one minute after application. CONCLUSION: The novel yeast extract rapidly relieves itch and is superior to the cosmetic market leader, CO lotion.

Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

Novel cannabidiol sunscreen protects keratinocytes and melanocytes against ultraviolet B radiation.

Cannabidiol (CBD), a natural occurring phytocannabinoid, is used extensively in consumer products ranging from foods to shampoos, topical oils and lotions. Several studies demonstrated the anti-inflammatory and antioxidative properties of cannabidiol. Nevertheless, the role of cannabidiol use in sunscreens is largely unknown as no studies on its effect on keratinocytes or melanocytes exist. As such, we aimed to explore the effect of CBD on keratinocyte and melanocyte viability following ultraviolet B (UVB) irradiation. CBD exhibited a dose-dependent protective effect on both keratinocytes and melanocyte viability. Further, since CBD does not demonstrate absorption in the UVB spectra, we speculate that the protective effect is due to reduction in reactive oxygen species. To our knowledge, this is the first study demonstrating the protective effect of CBD on keratinocytes and melanocytes irradiated with UVB.

Yeast extract demonstrates rapid itch relief in chronic pruritus.

BACKGROUND: Pruritus is the most common complaint encountered in dermatological practice. It is estimated that up to 4% of the world population suffers from chronic itch. Chronic pruritus can be associated with both cutaneous or systemic conditions. While a plethora of treatments attempt to address itch, most carry risk of significant adverse events with chronic use; thus, there exists an unmet need to develop safe treatments for chronic pruritus. A recent study demonstrated that a novel extract from Saccharomyces cerevisiae, that is, Baker's yeast, blocks various histamine receptors as well as inhibits numerous inflammatory cytokines. METHODS: Given the long-term safety profile of Baker's yeast, we set to investigate the efficacy of the novel extract in the treatment of chronic pruritus. KEY RESULTS: In our study, we demonstrated that within 30 minutes, the novel extract significantly reduced itch when compared to a placebo lotion (P = .0020). CONCLUSIONS: To our knowledge, this is the first study demonstrating that a novel extract from Saccharomyces cerevisiae can provide rapid and sustained itch relief to chronic pruritus patients.

[Duplication of the pituitary gland]. / Dvostruka hipofiza.

Duplication of the pituitary gland is a rare malformation. To the best of our knowledge, only 40 cases throughout the world have been reported previously. Due to associated severe developmental anomalies lots of these cases were diagnosed at autopsy. Only 7 patients survived beyond puberty, however, it is important to stress that none of them had major brain anomalies. We present the case of a girl with duplication of the pituitary gland (DPG), central precocious puberty and associated midline defects. Among fenestration of basilar artery, previously described in the literature, we also found, for the first time, a duplication of the M1-segment of the left median cerebral artery. Our patient is one of the 4 DPG patients with associated precocious puberty treated with gonadotropine releasing hormone agonists (GnRH), but the only one in whom this treatment was finished successfully.

Non-ablative radio frequency for the treatment of androgenetic alopecia.

INTRODUCTION: Medical treatment of androgenetic alopecia (AGA) is mainly limited to pharmacological and surgical interventions. Patients' desire for noninvasive and non-systemic treatments has accelerated research into medical devices that can promote hair growth. Low-level laser therapy (LLLT) was the first such device. However, its success has been limited by contradictory and often controversial efficacy claims. Work previously performed in animal models of AGA has demonstrated the viability of the wound repair mechanism as a potential treatment modality. This study therefore explores the use of a non-ablative radio frequency (RF) device in the treatment of AGA. METHODS: A single blindedstudy compared a non-ablative RF device versus a sham device in 24 men with AGA. Each subject received four treatments over the 12-week study. RESULTS: In this preliminary study of 24 AGA patients treated with a novel RF device, we demonstrated that 54% showed a clinical response. Furthermore, among patients that underwent four or more treatment sessions, 40% experienced a 30% or more increase in hair counts compared to baseline. CONCLUSIONS: If validated in a larger cohort, non-ablative RF may prove to be an important clinical tool in the treatment of AGA.

Novel shampoo reduces hair shedding by contracting the arrector pili muscle via the trace amine-associated receptor.

BACKGROUND: Approximately 40% of women experience excessive hair shedding when washing their hair. Previously, we have demonstrated that a topically applied α1 adrenergic receptor agonist can be used to contract the arrector pili muscle of the follicular unit (ie, produce "goose bumps"), increasing the force required to pluck hair by as much as 400%. Subsequently, we reported a topical cosmetic solution containing an α1 adrenergic receptor agonist that reduced hair shedding during brushing by a maximum of 77%. AIMS: In this communication, we explore a novel mechanism to contract the arrector pili muscle. Trace amine-associated receptors (TAAR) have been shown to regulate smooth muscle tone in blood vessels, but have not been reported to be present in the skin. Here, we report on the anti-shedding efficacy of a shampoo containing a selective TAAR agonist, tyramine hydrochloride. METHODS: A single-blinded crossover study was designed to test the efficacy of the novel shampoo versus placebo in reducing hairs lost during brushing. RESULTS: In this study, the novel TAAR shampoo reduced hair shedding during brushing by 31% in a cohort of 24 women with a maximum reduction of 77%. CONCLUSIONS: A shampoo formulated with a selective TAAR agonist was demonstrated to contract the arrector pili muscle and reduce hair shedding subsequent to washing.

TP53, Bcl-2 and growth hormone receptor expression in cutaneous squamous cell carcinoma.

The incidence and prevalence of premalignant and malignant skin lesions including squamous cell carcinoma (SCC) of the skin are increasing worldwide. The aim of the study was to determine TP53, Bcl-2 and growth hormone receptor (GHR) expression in SCC and to investigate relative importance of these proto-oncogenes in its biological behavior. Expression of TP53, Bcl-2 and GHR was determined by immunohistochemistry in 27 SCC specimens and adjacent perilesional skin. The relative proportion of immunoreactive cells was counted with semiquantitative method. TP53 positivity was detected in 24 (89%), Bcl-2 in 18 (67%) and GHR in 25 (93%) of 27 SCC specimens investigated. In comparison with perilesional skin, TP53 and GHR positivity was significantly increased, and Bcl-2 positivity significantly decreased in SCC. Increased TP53 expression in SCC lesions implies that Tp53 mutation is an early and crucial event in its development. Increased GHR expression suggests a role of growth hormone in the development of SCC.

Dental infection and dermatological diseases: analysis of ninety-two patients and review of the literature.

Dental disease has long been proposed as a potential causative agent in certain dermatological diseases. However, literature data on this association are scarce. The aim of this retrospective study was to evaluate dental status in 92 patients with various dermatological diseases who were referred to our Department for elimination of dental disease and to assess the relationship between dental infection and dermatological diseases. Dermatological conditions due to which patients were referred were alopecia, urticaria, eczematoid dermatitis, psoriasis, edema, etc. Out of 92 patients, 42 (45.7%) patients were referred for further dental treatment, while the remaining 50 (54.3%) patients had no observable dental pathology. None of the patients reported improvement following dental treatment. Based on the results of this study, we might conclude that dental infection does not play any role in the development of dermatological disease.