Olmsted syndrome (OS) is a rare genetic disorder, characterized by painful palmoplantar keratoderma (PPK), periorificial and intertriginous hyperkeratoses, and alopecia. Fewer than 75 cases have been described. Variants in TRPV3 result in constitutive activation of transient receptor potential vanilloid 3, leading to increased epidermal growth factor receptor (EGFR) signaling, palmoplantar epidermal hyperproliferation, and exquisite lesional pain. We describe pre-school aged twins with OS with partial improvement from oral erlotinib, an EGFR inhibitor, but dramatic reduction of their persistent palmoplantar thickening and pain from adding acitretin.

Infantile pustular psoriasis (IPP) is an extremely rare skin disease associated with genetic factors. Gene mutations of IL36RN (interleukin-36 receptor antagonist), CARD14 (caspase recruitment family member 14), and AP1S1 (the σ1C subunit of the adaptor protein complex 1) had been identified to be involved in the pathogenesis of IPP. IPP usually develops with no preceding psoriasis vulgaris (PV) or familial history. Here, we report a case of a 6-month-old infant and make the diagnosis of IPP by a series of examinations; subsequently, by detecting coexistent mutations of IL36RN and CARD14, the diagnosis is intensified from a genetic point of view. We treated the child with traditional oral and topical drugs regardless of the commonly used acitretin considering its potential side effects, such as skeletal toxicity, and the lesions got conspicuous improvement with much reduction of inflammation. Owing to the genetic mutation of IL-36, there had been reported cases focusing on anti-IL36 biological agents in the treatment of IPP, and it could be a new weapon to treat and improve such IL-36RN-deficient skin diseases.

Comel-Netherton syndrome, or Netherton syndrome (NS), is a rare chronic genetic skin condition affecting the daily life of patients, which often results in poorly developed social skills and anxiety. Genetic predisposition plays a key role alongside the clinical findings, and clinicians must be aware of it as it can mimic other well-known skin conditions. Diagnosis is challenging both clinically and histologically. Clinically, it can mimic a severe form of atopic dermatitis, psoriasiform dermatitis overlapping with atopic dermatitis, or erythrokeratodermia variabilis. The difficulties in making histological diagnosis are similar, and it is often necessary to take several biopsies in order to clarify the diagnosis. Although retinoids are used for both psoriasis, erythrokeratodermia variabilis, and other congenital forms of keratodermia, the recommended treatment doses are different. This often results in poor treatment outcome. We present a 16-year-old patient previously diagnosed as erythrokeratodermia variabilis and treated with little to no improvement. Systemic therapy with acitretin 10 mg daily, local pimecrolimus 1%, emollients, and bilastine 20 mg once daily was initiated. Due to the limited application of retinoids and the difficulties in achieving permanent remission, modern medicine is faced with the challenge of seeking innovative therapeutic solutions. New hopes are placed on targeted or anti-cytokine therapy, based on inhibiting the inflammatory component of the disease. This article is mainly focused on innovative therapeutic options, including modern medications such as dupilumab, infliximab, secukinumab, anakinra, omalizumab, and others.

To date, over 60% of the world's population has received at least 1 dose of coronavirus disease 2019 (COVID-19) vaccination, with over 12 billion doses administered globally. Commonly reported adverse effects of COVID-19 vaccination include fever, headache, myalgia, and injection site reactions. The spectrum of documented cutaneous reactions after COVID-19 vaccination is broad; however, pityriasis rubra pilaris (PRP) or PRP-like eruption secondary to COVID-19 vaccine is exceedingly rare, with only 17 cases previously reported to date in the English literature. In this article, we describe an additional case of COVID-19 vaccination-associated PRP in a 50-year-old woman with a history of metastatic breast carcinoma, who developed a widespread cutaneous eruption characteristic of PRP, including palmoplantar keratoderma, 10 days after her third dose of Moderna COVID-19 vaccine. Punch biopsy specimen showed epidermal hyperplasia with overlying hyperkeratosis, alternating orthokeratosis and parakeratosis and focal follicular plugging, supporting the diagnosis of PRP. The patient improved within weeks of initiating oral acitretin and topical steroids, with resolution achieved after 3 months of continued therapy. To the best of our knowledge, this is the third reported case of Moderna COVID-19 vaccination-associated PRP and collectively the 18th after the administration of all COVID-19 vaccines currently available, including Pfizer-BioNTech, and AstraZeneca.

Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.

Since Merkel cell polyomavirus (MCPyV) was linked as the predominant etiology of Merkel cell carcinoma (MCC) in 2008, three additional human polyomaviruses (HPyV) have been definitively linked to cutaneous diseases-trichodysplasia spinulosa virus (TSPyV) and human polyomavirus 6 and 7 (HPyV6, HPyV7). TSPyV contributes to the development of trichodysplasia spinulosa (TS), and HPyV6/7 is associated closely with the eruption of pruritic and dyskeratotic dermatoses (PDD). Clinically, MCC is treated with surgical excision and radiation with adjuvant chemotherapy, although newer treatment options include immune checkpoint inhibition. These novel immunotherapies hold promise for the treatment of metastatic MCC, but resistance and side effects prevent a significant proportion of patients from realizing their benefits. Based on previous case reports, the standard of care for the less deadly but disfiguring cutaneous disease TS include immunosuppressant (IS) reduction, the use of antivirals such as cidofovir (CDV) or valganciclovir (VGCV), or a combination of these treatments. Similar treatments were attempted for PDD, but oral acitretin was found to be most effective. As MCC, TS, and PDD are rare diseases, further research is required for effective treatments. In this review, we summarize clinical trials, preclinical studies, and case reports that present outcomes and side effects of current and emerging treatments for HPyV-associated cutaneous diseases, offering a comprehensive resource for clinical application and prospective clinical trials.

Generalized pustular psoriasis (GPP) is a rare and severe form of psoriasis presenting with erythematous, aseptic pustules. Common systemic symptoms include fever and myalgias. The presentation of GPP resembles acute generalized exanthematous pustulosis (AGEP). However, the treatment of these two pathologies differs. While AGEP is self-limiting and treated with topical corticosteroids and constrain of systemic steroids. GPP treatment avoids corticosteroid, choosing acitretin, methotrexate, and cyclosporine as first-line agents. In this case report, a 27-year-old female with a medical history of AGEP presented to the hospital with extensive erythema and pustules. Complete blood count acute phase reactant analysis revealed an elevated white blood cell count and C-reactive protein (CRP). Two histopathological examinations revealed psoriatic hyperplasia of the epidermis with keratosis, along with Kogoj and Munro micro abscesses above the spina layer. Lymphocytic and neutrophilic infiltrate was present in the superficial derma layer along with vasodilation. The patient was diagnosed with GPP according to pathological and clinical criteria. Treatment was initiated with secukinumab because of the patient's failure to respond to systemic treatment with Acitretin, methotrexate, and cyclosporin. Following 2 weeks of therapy with 300 mg of secukinumab, the pustular lesions had resolved. This study indicates the potential efficacy of secukinumab as an effective therapy that can rapidly improve the clinical symptoms of GPP.

Administration of systemic retinoids such as acitretin has not been approved yet for pediatric patients. An adverse event of retinoid-therapy that occurs with lower prevalence in children than in adults is hyperlipidemia. This might be based on the lack of comorbidities in young patients, but must not be neglected. Especially for the development of the human brain up to young adulthood, dysbalance of lipids might be deleterious. Here, we provide for the first time an in-depth analysis of the influence of subchronic acitretin-administration on lipid composition of brain parenchyma of young wild type mice. For comparison and to evaluate the systemic effect of the treatment, liver lipids were analogously investigated. As expected, triglycerides increased in liver as well as in brain and a non-significant increase in cholesterol was observed. However, specifically brain showed an increase in lyso-phosphatidylcholine and carnitine as well as in sphingomyelin. Group analysis of lipid classes revealed no statistical effects, while single species were tissue-dependently changed: effects in brain were in general more subtly as compared to those in liver regarding the mere number of changed lipid species. Thus, while the overall impact of acitretin seems comparably small regarding brain, the change in individual species and their role in brain development and maturation has to be considered.

Surgical intervention is seen as the gold standard in the treatment of Squamous cell carcinoma. Yet, in cases of recurrence, repeated surgical procedures may unwittingly foment the rise of reactive keratoacanthomas at the surgical margins or edge of a newly placed skin graft.

Acute generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis, characterized by an acute eruption of extensive erythema with numerous non-follicular pustules. In rare cases, local pustular psoriasis like acrodermatitis continua of Hallopeau (ACH) may progress into acute GPP if improperly treated. ACH and GPP are rare in the clinic and their treatment is more complex and often treatment-resistant compared to psoriasis vulgaris (PV). A variety of anti-psoriasis biologics emerging in recent years have been reported for the treatment of ACH and acute GPP. Biologics is considered to be an upgraded treatment option for traditional anti-psoriasis agents. But there are few reports of GPP patients developing resistance to biologics, or what if biologics fails. Herein, we report a case of acute GPP that developed from ACH, initially responded extremely well to adalimumab, but the treatment failed when the patient treated with the drug again, which is thought to have developed resistance to adalimumab, finally successfully treated with narrowband ultraviolet B (NB-UVB) and acitretin.

Subcorneal pustular dermatosis (SPD) is a rare, chronic pustular dermatosis. The pathogenesis of SPD has not been fully elucidated, but some studies have found that tumor necrosis factor (TNF)-α may be associated with its pathogenesis. Some patients with multidrug-resistant SPD have improved significantly after treatment with the anti-TNF-α agent (adalimumab). We present a case of a 28-year-old female with severe SPD who responded rapidly to adalimumab (80mg/week) in combination with acitretin and methylprednisolone within a week. With adalimumab (40 mg next week and followed by 40mg every two weeks) and gradually ceasing other systemic medication, the patient's condition continued to improve without relapse or side effects. The outcome of this case suggests that adalimumab might be an effective treatment option against multidrug-resistant SPD.

Psoriasis is chronic autoimmune disease that affects 2-5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU-ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box-Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU-ACT-coloaded NLCs. The FLU-ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU-ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of -34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU-ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU-ACT-coloaded NLCs and FLU-ACT-coloaded NLC gel compared with the FLU-ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU-ACT-coloaded NLC gel.

Psoriasis hospitalisation is not frequently reported. The objective of this study was to determine (1) the clinical, laboratory and treatment features of patients with psoriasis hospitalised due to flare-up and (2) other causes of admission of patients with psoriasis. We retrospectively reviewed data on 48 patients admitted due to psoriasis flare-up and 1908 patients with psoriasis admitted due to concomitant illnesses or comorbidities. The study period was 2005-2021. The latter group was compared with 821,804 patients without psoriasis admitted during the period. Of the 48 cases, 37.5% had erythroderma, and 62.5% had generalised pustular psoriasis (GPP). Women (68.8%) predominated, especially in the GPP group (76.7%). The mean age of admission with erythroderma (44.8 years) was higher than for GPP (32.1 years). Infection was the main trigger for psoriasis flare-up (46%). Abnormalities in liver function tests were found in 33.3% of the cases. These abnormalities usually subsided 1-2 months after skin improvement (83.4%). Acitretin was the most prescribed drug for GPP (81.4%), whereas topical treatment alone (50%) was the most frequent erythroderma therapy. Intensive care was needed by 9.3% of patients with GPP. In the psoriasis group admitted due to concomitant illnesses or comorbidities, admission due to digestive and infectious causes was significantly higher for psoriasis patients. Our study showed that trend of psoriasis admission due to disease flare-up was not significantly changed even in the era of biologics. We believed that patient education on avoiding the common precipitating factors of psoriasis flare-up and good self-care is mandatory to reduce the risk of hospitalisation.

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

We report a case of a 41-year-old male patient with no family history, presented with extensive multiple keratoacanthomas with disfiguring scars. The diagnosis of a sporadic form of Ferguson-Smith syndrome was made. Treatment with acitretin showed a marked response. Recognizing this syndrome is crucial. Early treatment helps avoid scar formation.

Acitretin belongs to a group of drugs known as retinoids. Retinoids include natural and synthetic compounds that have similar activity to vitamin A. Vitamin A helps regulate the immune system, impacts cellular growth, differentiation, proliferation, and plays a role in embryonic development. Other effects of retinoids include immunologic anti-inflammatory effects, induction of apoptosis, and inhibition of tumor promotion. This activity reviews the indications, contraindications, and adverse events associated with acitretin so that interprofessional team members can work together to manage patients using the medication optimally.