Perspectives on Psoriasiform Adverse Events from Immune Checkpoint Inhibitors: Lessons Learned from Our Practice.

Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.

A Rare Association of Disseminated Granuloma Annulare With Recurrent Uveitis.

Granuloma annulare is a benign chronic inflammatory granulomatous dermatosis with a variable clinical presentation. The disseminated form of the disease is characterized by a widespread papular eruption, primarily affecting the trunk, neck, and extremities. The development of granuloma annulare in patients with systemic diseases, such as diabetes mellitus, malignancy, or dyslipidemia, has been extensively documented. Still, only a few cases of granuloma annulare associated with recurrent uveitis have been reported. Herein, we present a rare case of generalized granuloma annulare that was associated with concomitant recurrent uveitis in a 60-year-old male patient with a history of type II diabetes mellitus. A general physical exam revealed widespread erythematous papules in an annular pattern on the trunk, characteristic of granuloma annulare. A series of tests were conducted, including autoimmune workup, all within normal limits. Histopathologic findings revealed features consistent with granuloma annulare. The patient was successfully treated with systemic corticosteroids for the uveitis and isotretinoin for the skin lesions. A close follow-up is recommended given the rare association of granuloma annulare and uveitis.

A Current Diagnostic and Therapeutic Challenge: Tinea Capitis.

Tinea capitis is a dermatophyte scalp infection with a marked prevalence among the pediatric population. However, in the last few years, its epidemiology has changed due to increasing population migration worldwide. Host-specific and environmental factors contribute to the pathogenesis of tinea capitis. Clinically, tinea capitis may present as a subtle hair loss accompanied by scalp scaling, alopecia with scaly patches, or alopecia with black dots. A more severe form of tinea capitis is represented by kerion celsi, which clinically presents as a tender plaque covered by pustules and crusts. If left untreated, this dermatophytic infection may resolve with permanent scarring and alopecia. The pathological changes found in tinea capitis are reflected by a spectrum of clinical changes. Zoophilic infections typically prompt an extensive inflammatory reaction, while anthropophilic dermatophytoses often lack inflammation and result in more persistent lesions. Tinea capitis typically requires systemic antifungal therapy. Griseofulvin, terbinafine, itraconazole, and fluconazole are the main antifungal agents used. Currently, the duration of antifungal therapy varies based on the clinical presentation and type of dermatophyte involved. Through the reported cases and literature review, we aim to emphasize the importance of the early recognition of atypical variants of tinea capitis in immunocompetent children for the prompt initiation of systemic antifungal therapy, minimizing the need for prolonged treatment. Additionally, we emphasize the importance of regular laboratory testing during systemic antifungal therapy, particularly liver enzyme tests, to prevent adverse events, especially in cases requiring long-term treatment.

Cutaneous Adverse Reactions Associated with Tattoos and Permanent Makeup Pigments.

Tattooing is the procedure of implanting permanent pigment granules and additives into the dermal layer of the skin, serving various purposes such as decoration, medical identification, or accidental markings. There has been a significant rise in the popularity of decorative tattooing as a form of body art among both teenagers and young adults. Thus, the incidence of tattoos is increasing, with expanding applications such as permanent makeup, scar camouflage, nipple-areola, lips, and eyebrows tattooing, and utilization in oncological radiotherapy such as colon marking. However, there have been reported a broad range of adverse reactions linked to tattooing, encompassing allergic reactions, superficial and deep cutaneous infections, autoimmune disorders induced by the Koebner phenomenon, cutaneous tumors, and others. These reactions exhibit different onset times for symptoms, ranging from immediate manifestations after tattoo application to symptoms emerging several years later. Given the limited information on a tattoo's side effects, this review aims to elucidate the clinical spectrum of cutaneous complications of tattoos in different patients. The analysis will investigate both allergic and nonallergic clinical presentations of tattoo-related side effects, microscopic findings from skin biopsies, and therapeutic outcomes. This exploration is essential to improve our understanding of tattoo-related cutaneous complications and associated differential diagnoses and highlight the significance of patient awareness regarding potential risks before getting a tattoo.

Recent-Onset Melanoma and the Implications of the Excessive Use of Tanning Devices-Case Report and Review of the Literature.

Introduction: Melanoma, a malignant tumor arising from uncontrolled melanocytic proliferation, commonly found in the skin but capable of affecting extracutaneous sites, ranks fifth among diagnosed oncological entities and is a significant cause of cancer deaths, constituting over 80% of skin cancer mortality. Genetic factors and ultraviolet radiation (UVR) exposure, from both natural and artificial sources, are the primary risk factors. Case Presentation: We reported the case of a 25-year-old female with numerous pigmented nevi and notable changes attributed to extensive indoor tanning sessions. Dermatological examinations and dermoscopic evaluations revealed atypical features in two pigmented nevi, leading to surgical excision. Histopathological and immunohistochemical analyses confirmed a compound nevus in one lesion and superficial spreading melanoma in the other, emphasizing the importance of vigilant follow-up and the correct use of immunohistochemistry. Discussion: Indoor tanning significantly elevates the cutaneous melanoma risk, with initiation before age 35 amplifying the risk by up to 75%, especially in young women. The risk escalates with cumulative sessions, particularly exceeding 480, and individuals undergoing over 30 sessions face a 32% higher risk. UVR induces DNA damage, genetic mutations, and immunosuppression, contributing to oncogenesis. Genetic factors, like the PTCHD2 gene, may influence the tanning dependency. Legislation targeting minors has been enacted globally but only with partial efficacy. Tanning accelerators, though associated with minor side effects, correlate with high-risk behaviors. The case underscores the urgency of addressing indoor tanning risks, emphasizing targeted awareness efforts and legislative improvements. Conclusions: In conclusion, the reported case highlights the increased risk of cutaneous melanoma linked to indoor tanning, particularly among young women and specific sociodemographic groups. Despite legislative measures, challenges persist, suggesting the potential efficacy of online campaigns involving relatable influencers to raise awareness and discourage artificial tanning.

Oxidative Stress and Inflammation Levels in a Population of Eastern European Naïve Versus Treated Psoriasis Patients.

Psoriasis is a chronic inflammatory disease, with a major impact on the patients' quality of life. Oxidative stress (OS) is represented by the imbalance between oxidant and antioxidant mechanisms of the organism, with increased levels being described in the majority of chronic diseases. We present the first prospective study in Romania to evaluate the redox balance changes (using a CR3000 analyzer) in patients with moderate-severe psoriasis based on treatment regimens: treatment-naïve (A), treatment with novel targeted agents (B) and methotrexate (C). The study group included 53 Caucasian patients divided into three groups (A- 27 patients, B - 15 patients, and C - 11 patients) for which OS, antioxidant status, standard blood count, and inflammatory status were evaluated. Our findings demonstrate that patients with psoriasis display high levels of OS, with elevated Free Oxygen Radical Test (FORT) (p-value for group A (pA)<0.0001, p-value for group B (pB)=0.0019 and p-value for group C (pC)=0.0063) and reduced Free Oxygen Radical Defense (FORD) (pB=0.018) values noted in our subjects. Higher erythrocyte sedimentation rate (ESR) values were detected in groups B (pB=0.00012) and C (pC<0.00001). Psoriasis treatments alleviate FORT and FORD levels, but their impact is not sufficient to restore the oxidative balance to normal ranges. Moreover, despite adequate treatment, patients with psoriasis display elevated inflammation levels. Future research should explore in more detail the interplay between OS and inflammation in psoriasis, namely the long-term impact on the redox balance of biotherapies.

An Insight on the Possible Association between Inflammatory Bowel Disease and Biologic Therapy with IL-17 Inhibitors in Psoriasis Patients.

Psoriasis is a chronic, inflammatory, multisystemic disease which affects approximately 2-3% of the population globally, whose onset is triggered by genetic and environmental factors which activate both dendritic cells and keratinocytes, resulting in the production of proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 17, interleukin 23, interleukin 22, and interleukin 1ß. An in-depth understanding of the pathophysiology of psoriasis led to significant advances in the development of safe and efficient novel therapeutic options, with four classes of biologic therapy being approved for the management of moderate to severe psoriasis: tumor necrosis factor alpha inhibitors, interleukin 23 inhibitors, anti-interleukin 12/23 agents, anti-interleukin 17 agents, as well as small-molecule inhibitors, such as apremilast. Psoriasis is associated with comorbid conditions, namely psoriatic arthritis, cardiovascular disease, metabolic syndrome, psychiatric disorders, malignancy, as well as inflammatory bowel disease. For patients affected by both psoriasis and inflammatory bowel disease, there is a strong recommendation to avoid IL-17 inhibitors since they may play a part in the exacerbation of the gastrointestinal disease. Our aim was to perform a thorough literature review regarding the development of inflammatory bowel disease lesions in psoriasis patients treated with IL-17 inhibitors, along with a case presentation to emphasize the need for close follow-up of these patients.

Cutaneous Melanoma and Glioblastoma Multiforme Association-Case Presentation and Literature Review.

The occurrence of both melanoma and glioma was first suggested by the observation of a familial association between these conditions, which was later confirmed by the description of the melanoma-astrocytoma syndrome, an extremely rare, inherited affliction in which people have an increased risk of developing melanoma and nervous system tumors. Taking into consideration the common embryologic precursor, the neuroectoderm, it was hypothesized that this syndrome is associated with a genetic disorder. While some families with germline CDKN2A mutations are prone to develop just melanomas, others develop both melanomas and astrocytomas or even other nervous-system neoplasms. Herein, we report the case of a 63-year-old male patient with no personal or family history of malignancy who had primary melanoma followed by glioblastoma. Our case report suggests that the occurrence of both melanoma and glioblastoma is most likely not coincidental but instead linked to genetic mutations of common embryologic precursors or signaling pathways.

Challenging Patterns of Atypical Dermatofibromas and Promising Diagnostic Tools for Differential Diagnosis of Malignant Lesions.

Dermatofibroma (DF) or fibrous histiocytoma is one of the most frequent benign cutaneous soft-tissue lesions, characterized by a post-inflammatory tissue reaction associated with fibrosis of the dermis. Clinically DFs have a polymorphous clinical aspect from the solitary, firm, single nodules to multiple papules with a relatively smooth surface. However, multiple atypical clinicopathological variants of DFs have been reported and, therefore, clinical recognition may become challenging, leading to a more burdensome identification and sometimes to misdiagnosis. Dermoscopy is considered an important tool in DFs diagnosis, as it improves diagnostic accuracy for clinically amelanotic nodules. Although typical dermoscopic patterns are most frequently seen in clinical practice, there have also been some atypical variants described, mimicking some underlying recurrent and sometimes harmful skin afflictions. Usually, no treatment is required, although an appropriate work-up may be necessary in specific cases, such as in the presence of atypical variants or a history of recent changes. This narrative review's aim is to summarize current evidence regarding clinical presentation, positive and differential diagnosis of atypical dermatofibromas and also to raise awareness about the importance of specific characteristics of atypical variants to better differentiate them from malignant conditions.

Current and Future Approaches in Management of Chronic Spontaneous Urticaria Using Anti-IgE Antibodies.

Chronic spontaneous urticaria (CSU) considerably alters patients' quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms "anti-IgE antibodies", "omalizumab", "ligelizumab", and "chronic spontaneous urticaria". The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients' quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.

Risks of Biologic Therapy and the Importance of Multidisciplinary Approach for an Accurate Management of Patients with Moderate-Severe Psoriasis and Concomitant Diseases.

Psoriasis is a chronic multisystem inflammatory disease associated with a plethora of comorbidities including metabolic syndrome, cardiovascular disease, hypertension, diabetes, hyperlipidemia, obesity, anxiety, depression, chronic kidney disease, and malignancy. Advancement in unveiling new key elements in the pathophysiology of psoriasis led to significant progress in the development of biologic agents which target different signaling pathways and cytokines involved in the inflammatory cascade responsible for the clinical manifestations found in psoriasis. Currently available novel therapeutic options for moderate-severe psoriasis include tumor necrosis factor alpha inhibitors, inhibitors of the interleukin 17, and inhibitors of the interleukin 23. Nevertheless, concerns have been raised with respect to the possible risks associated with the use of biologic therapy requiring close collaboration between dermatologists and physicians of different specialties. Our aim was to perform an in-depth literature review and discuss the potential risks associated with biologic therapy in patients with psoriasis and concurrent diseases with a focus on the influence of novel therapeutic agents on liver function in the context of hepatopathies, particularly viral hepatitis. A multidisciplinary teamwork and periodic evaluation of psoriasis patients under biologic therapy is highly encouraged to obtain an accurate management for each case.

A Rare Case of Neglected Giant Basal Cell Carcinoma in a Nurse-Case Report and Literature Review.

Basal cell carcinoma (BCC) is the most common skin cancer in the fair-skinned adult population over 50 years of age and the incidence is rising. Generally, BCC has an indolent course, low mortality and a good prognosis due to low rates of metastasis. Giant basal cell carcinoma is a rare reported oncological entity which accounts for 0.5% to 1% of all cases of BCC and has a diameter larger than 5cm. Basosquamous carcinoma is a rare high-risk type of BCC with clinical and histopathological features of both BCC and squamous cell carcinoma. A 61-year-old female presented to our clinic for a giant bleeding tumor located under her left breast. She initially noted the tumor almost 15 years ago. Although the patient was a nurse, she was afraid to seek medical advice until an episode of significant bleeding. At presentation the tumor was a 15/7cm in size, was invading the underlying structures and had a central ulceration. The margins of the tumoral plaque had several nodules and pearly structures suggesting the possible clinical diagnosis of BCC.

Electrochemotherapy and Other Clinical Applications of Electroporation for the Targeted Therapy of Metastatic Melanoma.

Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be used as an alternative for oncologic patients not eligible for surgery or other standard therapies. Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location. Skin neoplasms are the main clinical indication of ECT, the procedure reporting good curative results and high efficiency across all tumor types, including melanoma. In daily practice, there are many cases in which the patient's quality of life can be significantly improved by a safe procedure such as ECT. Its popularity must be increased because it has a safe profile and minor local adverse reactions. The method can be used by dermatologists, oncologists, and surgeons. The aim of this paper is to review recent literature concerning electrochemotherapy and other clinical applications of electroporation for the targeted therapy of metastatic melanoma.