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Sweet's syndrome, also known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory condition. It is considered to be the prototype disease of neutrophilic dermatoses, and presents with acute onset dermal neutrophilic lesions, leukocytosis, and pyrexia. Several variants have been described both clinically and histopathologically. Classifications include . The cellular and molecular mechanisms involved in Sweet's syndrome have been difficult to elucidate due to the large variety of conditions leading to a common clinical presentation. The exact pathogenesis of Sweet's syndrome is unclear; however, new discoveries have shed light on the role of inflammatory signaling, disease induction, and relationship with malignancy. These findings include an improved understanding of inflammasome activation, malignant transformation into dermal infiltrating neutrophils, and genetic contributions. Continued investigations into effective treatments and targeted therapy will benefit patients and improve our molecular understanding of inflammatory diseases, including Sweet's syndrome.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by chronic, painful ulcerations. Despite increasing evidence suggesting immunological dysregulation, the role of IL-36 cytokines in PG remains poorly defined. To evaluate serum levels of IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38 in PG patients compared to healthy controls, and to assess their correlation with selected clinical parameters and cytokine ratios. 44 PG patients and 40 healthy controls were included in this case–control study. Serum cytokine levels were measured using ELISA. Correlations between cytokine levels and clinical features were analyzed using nonparametric tests. PG patients showed significantly lower serum levels of IL-36α and IL-36γ (p = 0.0003 and p = 0.02, respectively), with no difference in IL-36β. Conversely, levels of IL-36Ra, IL-37, and IL-38 were significantly higher in PG patients (p < 0.0001 for all). In the PG group, significant positive correlations were observed between IL-36α and IL-36β, and between IL-36β and IL-36γ, while IL-37 correlated negatively with IL-38. IL-36α was inversely associated with serum IgA levels and total ulcer surface area, and IL-36γ correlated negatively with white blood cell count. Our findings reveal a dysregulated IL-36 cytokine profile in pyoderma gangrenosum, marked by reduced serum levels of IL-36α and IL-36γ and elevated levels of IL-36Ra, IL-37, and IL-38. This may reflect a compensatory response to chronic inflammation. The inverse correlation between IL-36α and ulcer size suggests its potential involvement in wound healing. Despite lower serum levels of agonists, local biological activity of IL-36 cytokines may remain elevated due to tissue-level activation and consumption. These results highlight the therapeutic relevance of targeting the IL-36 pathway—particularly in treatment-resistant cases—and support further research into cytokine activity beyond serum concentration to guide novel therapeutic strategies.

Tumors diagnosed in the entire study cohort Cancer sites Cases n % Male cases, n Female cases, n Neutrophilic dermatoses Cases, n Plaque psoriasis Cases, n No cancer 229 82.4 112 117 41 188 Oral cavity 1 0.4 – 1 1 – Stomach 4 1.4 4 – 3 1 Colon 3 1.1 1 2 1 2 Liver, biliary tract 3 1.1 3 – 1 2 Lung 5 1.8 4 1 1 4 Skin (keratinocytic) 7 2.5 4 3 1 6 Breast 8 2.9 1 7 1 7 Uterus (body) 1 0.4 – 1 – 1 Prostate 2 0.7 2 – – 2 Kidney 3 1.1 3 – – 3 Urotheliala 6 2.2 5 1 1 5 Central nervous system 3 1.1 – 3 - 3 Non-Hodgkin lymphomas 1 0.4 1 – – 1 Myelodysplastic syndromes 1 0.4 1 – – 1 Non-specified site 1 0.4 1 – 1 – Total 49 17.6 30 19 11 38 Bold represents the amount of these percentages Italic represents the percentage of cases described aRenal pelvis, ureter, bladder, urethra (uncertain malignant potential, in situ, invasive) A first remarkable finding was that the whole cohort experienced a 31% global excess of cancer risk with respect to the age-matched general population living in the same area (Table 2). Cancer incidence risk in the cohort patients Incident cancers, n Person years1 SIR2 CI95% AR3 Are (%)4 Total 49 3005 1.31 0.97–1.73 9.2 57 Males 30 1423 1.48 1.0018–2.12 12.5 59 Females 19 1582 1.10 0.66–1.72 60.0 50 Diagnosis5 0–54 years 9 1162 2.14 0.98–4.07 5.5 72 55 + years 40 1843 1.21 0.86–1.64 3.1 14 Neutrophilic dermatoses 11 571 1.35 0.68–2.42 10.7 55 Plaque psoriasis 38 2435 1.30 0.92–1.79 9.6 61 Cutaneous carcinoma6 7 3005 1.03 0.42–2.13 0.7 32 Female breast cancer 7 1582 1.64 0.66–3.39 2.5 58 Significant values are reported in bold Italic is used only to distnguish percentage from absolute values 1From Ferrara Unit of Emilia-Romagna Cancer Registry 1995–2017 (70,181 incident cases; 8,113,698 p*y) 2Standardized Incidence Ratio (observed/expected*) 3Attributable risk × 1000 4Attributable risk in exposed (cohort) 5Age at histological diagnosis of neutrophilic dermatosis/plaque psoriasis 6Keratinocytic forms With respect to the main study objective, the increased cancer risk among patients with neutrophilic dermatoses (SIR 1.35, CI 95% 0.7–2.4), when compared with the general population, did not differ significantly from that of patients with plaque psoriasis (SIR 1.30, CI 95% 0.9–1.8) both in univariate and multivariate Cox model. Prevalence, incidence, and risk of cancer in patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

Skin lesions have been reported in about 10–12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet's disease, Sweet's syndrome, adult-onset Still's disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis strongly associated with inflammatory bowel disease (IBD). This narrative review summarizes current knowledge on the epidemiology, clinical features, proposed mechanisms, and treatment of PG in patients with IBD. In addition to population-based, large cohort, and mechanistic studies, we reviewed 115 published case reports and case series describing patients with PG and IBD and synthesized demographic, clinical, and therapeutic trends. Most patients developed PG after an IBD diagnosis, with smaller proportions presenting simultaneously or before an IBD diagnosis. PG in IBD patients typically affects middle-aged adults and has a female predominance. Clinical features are heterogeneous, which complicates recognition and timely diagnosis. Treatment responses are also highly variable. Corticosteroids and immunosuppressants are commonly used as first-line therapies, but many patients require sequential or combined regimens. Biologics are increasingly used, reflecting efforts to target shared inflammatory pathways between PG and IBD; however, treatment approaches remain highly individualized. Mechanistic and genetic studies implicate Th17/Th1 immune dysregulation, IL-1β/IL-36 signaling, and gut-skin immune crosstalk. There is a critical need for longitudinal, controlled studies to clarify pathogenesis, predict outcomes, and guide evidence-based, standardized treatment approaches in this complex patient population.

Pyoderma gangrenosum is a neutrophilic dermatosis characterized by rapidly progressing inflammatory skin lesions. It is often associated with underlying systemic conditions, such as inflammatory bowel disease and rheumatoid arthritis. Patients typically present with erythematous papules and pustules that rapidly evolve into painful ulcers, most commonly affecting the lower extremities. In this case report, we describe a 57-year-old female patient with multirefractory pyoderma gangrenosum localized to the lower left leg. The diagnosis was confirmed based on clinical and histopathological features, with a skin biopsy showing compatible findings. Initial treatments, including topical therapies (high-potency steroids, dapsone, and calcineurin inhibitors) and conventional systemic immunosuppressive therapies (corticosteroids and tumor necrosis factor inhibitors), failed to produce significant improvement. However, treatment with risankizumab, an interleukin-23 inhibitor, resulted in substantial ulcer healing over a few weeks and ultimately led to complete resolution.

Introduction Pyoderma gangrenosum (PG) can represent a diagnostic challenge, leading to missed or delayed diagnosis. With prolonged immunosuppressive therapy, the risk of infections is elevated, predisposing patients to receive anti-infective treatments and, in serious cases, amputations. Limb amputations have been reported as complication of PG misdiagnosis but can also occur as a complication of long-standing PG ulcers. Methods We aimed to describe the clinical characteristics of patients with PG leading to limb amputation through a multicenter retrospective case series between 2010 and 2020 including patients with PG who underwent limb amputation. We report a descriptive analysis of these patients’ clinical course and outcome. Results Ten patients with PG who underwent at least one limb amputation were identified. Six were male (60%). Mean age was 65 years. All patients had ulcerative PG on the lower extremities, with a mean PG ulcer duration of 30.6 months. Six patients had PG-related comorbidities such as ulcerative colitis, myelodysplasia, and inflammatory arthritis. Other significant comorbidities included diabetes mellitus (DM) (five patients), coronary artery disease (five patients), and chronic kidney disease (two patients). The majority of patients (8/10) were correctly diagnosed with PG prior to amputation, whereas two patients were misdiagnosed with necrotizing soft tissue infections (NSTIs). All patients received intravenous antibiotics without substantial improvement. Eight patients developed sepsis and shock-like symptoms and the diagnosis of NSTIs was considered. Below-knee amputation was performed in six patients and above-knee amputation in four. Four patients had amputation performed twice because of recurrent NSTIs. Conclusion This multicenter case series sheds light on practice gaps for physician assessing patients with PG, in that limb amputation may result from PG misdiagnosis or complications thereof. Elderly patients (above 65 years) with coexisting lower extremity PG, DM, and/or chronic cardiac or renal disease should be managed with particular care toward preventing infection/NSTIs to prevent further complications such as limb amputations.

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients’ quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980–September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy. Plain Language Summary Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients’ quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.

The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation. A point mutation in this gene (Ptpn6spin) causes spontaneous inflammation in mice, which has a striking similarity to neutrophilic dermatoses in humans. Recent findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice; however, the underlying transcriptional regulation is poorly understood. Here, we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin mice. Moreover, we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory genes. Furthermore, Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin mice. Overall, in addition to its well-known role in driving inflammation in cancer, Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.