Search Results (10)

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal barrier dysfunction and immune dysregulation, with interleukin (IL)-4, IL-13, and IL-31 recognized as key mediators. Prurigo nodularis (PN) is another chronic inflammatory disorder driven by T helper type 2-mediated inflammation and neural dysregulation, leading to severe pruritus. Nemolizumab, a humanized monoclonal antibody targeting IL-31 receptor A, has been approved for use in the treatment of AD and PN. Clinical trials have demonstrated significant reductions in pruritus and cutaneous symptoms associated with its use. In clinical practice, acute eczema and edematous erythema frequently occur, occasionally necessitating the discontinuation of treatment. Despite these observations, no comprehensive review has examined nemolizumab-associated cutaneous adverse events. This review aimed to examine various cutaneous reactions associated with nemolizumab therapy, including psoriasiform eruptions, AD exacerbation, bullous pemphigoid, drug-induced eruptions, and fungal infections. Potential mechanisms underlying these reactions include T-cell activation due to drug sensitization, immune responses triggered by nemolizumab acting as a hapten, and a relative increase in IL-4 and IL-13 levels following IL-31 inhibition. However, the precise pathophysiological mechanism and risk factors remain unclear, and standardized clinical management guidelines are lacking. Further accumulation of clinical data and immunological research are essential for developing evidence-based strategies to manage these adverse events, ensuring treatment continuity and optimizing patient outcomes. Full article

Introduction: Psoriasis (PSO) and atopic dermatitis (AD) have traditionally been considered distinct diseases, respectively, mediated by T-helper 1 (Th1) and the T-helper 2 (Th2) immune pathway. In recent years, there has been a growing body of evidence highlighting an overlap between the two conditions, such as Asian AD, pediatric PSO, or “psoriasis dermatitis/PSOREMA”. Moreover, psoriasis dermatitis can be induced by therapeutic interventions. For instance, anti-IL-4/IL-13 monoclonal antibodies, commonly used to treat AD, can induce psoriasiform reactions by inhibiting the Th2 pathway, thereby unmasking Th1/Th17-driven PSO. Conversely, anti-TNFα and anti-IL-17 therapies, effective for PSO, may induce eczematous reactions promoting a switch toward Th2-driven inflammation. Janus Kinase Inhibitors (JAK-i) and IL-23 antagonists may represent valid therapeutic options for managing psoriasis dermatitis. JAK-i exert broader immunomodulatory effects, inhibiting both Th1 and Th2 pathways; however, they require careful monitoring due to potential adverse events. In contrast, IL-23 antagonists specifically suppress the IL-23/IL-17 axis inhibiting the p19 subunit of IL-23 and could represent a safer option for patients with psoriasis dermatitis. Materials and Methods/Results: We present a series of five cases of psoriasis dermatitis, including both patients who had the condition from the onset and those who developed it during treatment, with tailored therapeutic strategies based on individual patient profiles, comorbidities, and the specific characteristics of their overlapping disease presentation. Conclusion: JAK-i and IL-23 antagonists are both valid therapeutic options for managing psoriasis dermatitis, but with different immunomodulatory effects and safety profiles. Future research should focus on a better understanding of the immune pathway and identifying specific biomarkers of psoriasis dermatitis, to optimize therapeutic strategies. Full article

Background/Objectives: The landscape of advanced melanoma treatments has shifted dramatically in recent years. Target therapy and immunotherapy have changed the management of patients with both metastatic (stage IV according to AJCC 8th ed.) and nodal (stage IIB/C and III) disease. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, high-grade or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining a patient’s quality of life is of paramount importance. Methods: We undertook a prospective, monocentric, and descriptive study in Bologna, Italy, including patients referred to the Oncologic Dermatology Unit of IRCCS AOU of Bologna who developed biopsy-proven cutaneous adverse events (AE) under treatment with immunotherapy for cutaneous melanoma with nodal (stage IIB/C, III) and metastatic (stage IV) disease from January 2016 to April 2024. Results: In 202 identified patients, 75 (37.5%) developed skin AEs. Ipilimumab was causal for 48.1% of skin AEs, followed by nivolumab (37%) and pembrolizumab (31.4%). Recorded types of skin AEs included erythematous rash, vitiligo, alopecia, lichenoid, maculopapular, acneiform, urticarial, psoriasiform, granulomatous, eczematous, and severe cutaneous AEs, such as Erythema multiforme/Stevens-Johnson syndrome and bullous autoimmune dermatoses. Most AEs were low-grade [CTCAE 1–2] (97%) and typically occurred after 10 weeks of treatment. Conclusions: This study comprehensively describes skin AEs occurring during systemic treatment with ICIs for cutaneous melanoma at a single center. Full article

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. Full article

Background: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. Methods: Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords “ustekinumab” or “Stelara” in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. Results: Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. Conclusions: Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings. Full article

Recent progress in the treatment of advanced melanoma has led to the improved survival of affected patients. However, novel treatments also lead to considerable and distinct skin toxicity. To further characterize cutaneous adverse events (AE) of systemic treatments, we conducted a single-center retrospective study of biopsy-proven cutaneous adverse events of melanoma treatment over a period of 10 years at the University Hospital of Zurich, Switzerland. In 102 identified patients, 135 individual skin AEs developed. Immune checkpoint blockade (ICB) was causal for 81 skin AEs, and 54 were related to targeted therapies (TT). Recorded types of skin AEs included lichenoid, maculopapular, acneiform, urticarial, panniculitis, folliculitis, psoriasiform, granulomatous, eczematous, and others. The incidence of skin AEs was higher with TT (18.54%) than with ICB (9.64%, p = 0.0029). Most AEs were low-grade, although 19.21% of AEs were common terminology criteria for adverse events (CTCAE) Grades 3 or 4. A large spectrum of skin AEs was documented during treatment of advanced melanoma, and distinct phenotypes were observed, depending on treatment classes. AEs occurred earlier during treatment with TT than with ICB, and distinct types of skin AEs were associated with respective treatment classes. This study comprehensively describes skin AEs occurring during systemic treatment for melanoma at a single center. Full article

Immune checkpoint blockers (ICBs) have been widely used during the last decade for the treatment of various tumors, including advanced and metastatic melanoma. While these agents have improved melanoma patients’ survival rates, they have also been associated with various autoimmune toxicities, with the skin being most commonly affected. The severity of cutaneous toxicity can not only negatively affect patients’ quality of life but can also limit the proper treatment of cancer. Thus, the role of the dermatologist is substantial in early detecting and promptly treating these adverse events. Maculopapular rash, psoriasiform, lichenoid dermatoses and bullous pemphigoid are the most frequent cutaneous adverse events that require immediate intervention. Other rare autoimmune toxicities, e.g., sarcoidosis, dermatomyositis or subacute lupus, have also been reported. In this review, we summarize the aspects of ICB-induced cutaneous toxicities in patients with melanoma, emphasizing their management and treatment options in clinical practice. Full article

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first isolated in Wuhan, China, is currently a pandemic. At the beginning of the pandemic, pulmonary issues were the most discussed and studied. However, now 3 years later, the role of the dermatologist has become increasingly central. Often the diversity in the presentation of these manifestations has made it difficult for the dermatologist to recognize them. In addition to the common symptoms involving fever, cough, dyspnea, and hypogeusia/hyposmia that have been widely discussed in the literature, much attention has been paid to dermatologic manifestations in the past year. The vaccination campaign has been the most important strategy to combat the COVID-19 pandemic. Specifically, two viral vector-based vaccines [Vaxzervria^® (AstraZeneca; AZD1222) and COVID-19 Janssen^® vaccine (Johnson & Johnson; Ad26.COV2. S)] and two mRNA-based vaccines [Comirnaty^® (Pfizer/BioNTech; BNT162b2) and Spikevax^® (Moderna; mRNA-1273)]. However, several cutaneous adverse reactions have been reported following vaccination, making the dermatologist’s role critical. It is possible to group these adverse reactions according to a classification with six main clinical pictures: urticarial rash, erythematous/maculopapular/morbid rash, papulovesicular rash, chilblain-like acral pattern, livedo reticularis/racemose-like, and purpuric “vasculitic” pattern. Beyond this classification, there are several reports of other dermatologic manifestations associated with the infection, such as pityriasis rosea, herpes zoster, or, particularly, the worsening of pre-existing chronic inflammatory dermatologic diseases. Here we report the case of a 61-year-old patient who presented at our clinic with a diffuse psoriasiform eruption mixed with a concomitant blistering rash induced by COVID-19. The uniqueness of our case has two features: the first is the concomitance of the two events after infection that seems to be unprecedented; the second is the management of the patient that could help dermatology colleagues in the management of these conditions during infection. Full article

Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. The understanding of ICI-induced inflammatory eruptions with detailed histopathological findings is not adequate, particularly in Asian populations. In this study, we retrospectively reviewed 51 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Of the 51 patients (30 men, 21 women), maculopapular rash (38/51, 74.5%), erythema multiforme (2/51, 3.9%), lichenoid reaction (3/51, 5.9%), psoriasiform reaction (3/51, 5.9%), bullous pemphigoid (3/51, 5.9%), scleroderma-like reaction (1/51, 2.0%), and Stevens–Johnson syndrome (1/51, 2.0%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 months). With appropriate treatment and/or interruption of ICIs, most rashes improved (50/51, 98.0%). The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous irAEs. Full article

Interferons are widely used platform therapies as disease-modifying treatment of patients with multiple sclerosis. Although interferons are usually safe and well tolerated, they frequently cause dermatological side effects. Here, we present a multiple sclerosis (MS) patient treated with interferon-β who developed new-onset psoriasis. Both her MS as well as her psoriasis finally responded to treatment with fumarates. This case illustrates that interferons not only cause local but also systemic adverse events of the skin. These systemic side effects might indicate that the Th17/IL-17 axis plays a prominent role in the immunopathogenesis of this individual case and that the autoimmune process might be deteriorated by further administration of interferons. In conclusion, we think that neurologists should be aware of systemic cutaneous side effects and have a closer look on interferon-associated skin lesions. Detection of psoriasiform lesions might indicate that interferons are probably not beneficial in the individual situation. We suggest that skin lesions may serve as biomarkers to allocate MS patients to adequate disease-modifying drugs. Full article