Necrotizing periorbital Sweet syndrome is an uncommon mimic of necrotizing fasciitis that requires contrasting management. We describe a 60-year-old man with rapidly progressive unilateral eyelid edema, pain, and necrosis unresponsive to broad-spectrum antibiotics. Computed tomography showed periorbital soft-tissue swelling with gas. Two debridements for presumed necrotizing fasciitis yielded "dishwater" fluid; histopathology and special stains revealed a dense neutrophilic dermatosis without organisms, and cultures grew only commensals. He improved promptly after high-dose corticosteroids. Hematologic evaluation for escalating leukocytosis uncovered acute myeloid leukemia with t(6;9) and neuroblastoma RAS viral oncogene homolog mutation. A targeted literature synthesis showed frequent initial misdiagnoses as cellulitis or necrotizing fasciitis, unnecessary debridement, common association with myeloid neoplasia, and rapid steroid response. Periorbital sweet syndrome should be considered when cultures are sterile and clinical status worsens despite antibiotics; early biopsy and empiric corticosteroids can avert morbidity and unmask occult malignancy.

An Acute Onset Sweet Syndrome After First Vedolizumab Dose in Crohn's Disease.

Abstract A 5‐year‐old, neutered, male Australian shepherd dog was presented with a week‐long history of fever, lethargy and hyporexia. Physical examination revealed an enlarged right retropharyngeal lymph node and multifocal, painful, non‐pruritic pustular skin lesions on the distal joints of all four limbs. Computed tomography identified a heterogeneously enhancing mass in the right retropharyngeal lymph node. Histopathology confirmed a nodal haemangiosarcoma, presumed to be the primary tumour in the absence of other detectable lesions. Skin biopsies revealed neutrophilic dermatitis consistent with Sweet syndrome. Surgical excision of the lymph node was followed by adjuvant chemotherapy with doxorubicin and concurrent glucocorticoids, leading to complete resolution of the skin lesions. Six months later, similar dermatological signs reappeared. A follow‐up computed tomography revealed metastases to the lymph nodes, spleen, liver and bones, along with a cutaneous relapse, reinforcing a paraneoplastic association. The dog was euthanased 470 days after initial diagnosis due to a pathological femoral fracture.

Background. In this study, we performed ultrasound (US) evaluation of the ankles in patients with acute-onset erythema nodosum (EN) and joint symptoms to characterize the US features of this common manifestation and to assess whether these findings could help differentiate Löfgren’s syndrome (LS) from other conditions. Materials and Methods. Thirteen consecutive patients with acute onset of EN and mono- or bilateral ankle involvement (arthralgia/arthritis/swelling) were recruited at a single rheumatologic centre. All patients underwent specific diagnostic investigations aimed at identifying the cause of EN, separating those cases in which it was a manifestation of LS from those in which it was secondary to other causes (OC). An experienced operator in musculoskeletal US, blinded to the course of the diagnostic work-up, performed US examination of ankles bilaterally, investigating the presence of the following parameters: (a) Joint effusion/synovitis at tibiotalar joint (TT JEP); (b) Tenosynovitis (TS) at anterior (AC), lateral (LC) and medial compartment (MC) level; (c) Soft cutaneous tissue inflammation (SCTI) around the ankle. All parameters were initially scored according to OMERACT definition, both for grey scale (GS) and Power Doppler (PD), except for SCTI which were scored according to GLOUDAS definition. US features were classified as positive if their OMERACT parameters were GS>=2 and PD>=1 and if GLOUDAS GS and PD SCTI were >=1. Chi-square test was performed to assess the association between patients diagnosed with LS and US findings. Results. At the end of the diagnostic workup, 8 patients were diagnosed with LS; whereas the remaining patients received diagnosis of mediastinal lymphoma, Sweet's syndrome during pregnancy, EN secondary to Chron's disease, reactive manifestation during M. homini infectiction and one case remained idiopathic. Demographic and clinical details of the recruited cohort are reported in table 1. Mean time of the US examination was 5 minutes. The prevalence and comparison of US findings in the whole group, in LS group and in OC group are shown in table 2. In particular, within the comparison of LS vs OC, we found a higher prevalence of bilateral positive SCTI, MC and LC compartment TS in the LS group. At statystical analysis, bilateral TS of MC and bilateral SCTI were associated with LS (p<0.095 and p<0.001 respectively) while no statystical difference was found for TT JEP between the two groups. Conclusions. Despite widely considered as arthritis for its clinical appareance, our study shows how the typical ankle involvement in LS is characterised by a periarticular inflammation, tipically involving soft tissue and tendons without involving talo-navicular joint. Identifying those features with a rapid US ankles assessment in patients with new diagnosis of EN, may raise suspicion for LS, addressing diagnostic and therapeutic workup even during a outpatient visit.

ABSTRACTSweet syndrome, or acute febrile neutrophilic dermatosis, is an uncommon inflammatory condition that may arise secondary to infection, malignancy, autoimmune disease, or drugs. Its association with tuberculosis is rare, and rifampicin‐induced Sweet syndrome has been infrequently reported. We present a 58‐year‐old man with disseminated tuberculosis who developed painful erythematous plaques shortly after commencing antituberculous therapy (ATT). The eruption improved with corticosteroids but recurred specifically on rechallenge with rifampicin, confirming a drug‐induced aetiology. Rifampicin was excluded, and the patient completed ATT successfully with the remaining first‐line drugs. Rifampicin‐induced Sweet syndrome is a rare but important differential in patients who develop erythematous plaques on ATT. Accurate diagnosis allows continuation of essential tuberculosis treatment while avoiding unnecessary discontinuation of other first‐line drugs.

IDH1/2-mutant clonal hematopoiesis: A novel driver of autoinflammatory disease

This letter highlights recent mechanistic insights into Sweet syndrome, focusing on the IL-36–PADI4 inflammatory circuit that links neutrophil activation, NETosis, and keratinocyte signaling. We discuss how these findings redefine the immunopathogenesis of neutrophilic dermatoses and identify remaining challenges in translating IL-36–targeted therapies to clinical practice.

Abstract Introduction Chronic recurrent multifocal osteomyelitis (CRMO) is a sterile, autoinflammatory condition of bone that affects children and adolescents and presents with bone pain, bony tenderness or swelling. It can be associated with other inflammatory conditions including inflammatory bowel disease, Takayasu’s arteritis, palmo-pustular psoriasis, acne, pyoderma gangrenosum, sweet syndrome and sclerosing cholangitis to name a few. The importance of this is to consider these other conditions when a patient has symptoms suggestive of those with a background of CRMO, or the other way round. Case description Our patient was a 11-year-old boy at presentation, had been previously fit and well with unknown family history as he was adopted. He presented to paediatrics with right sided hip pain which had begun to limit his physical activity and inconsistent history of night pain. He was pale with restriction of movements of right hip and forward flexion of spine with tight hamstrings and no other significant physical findings. He had an MRI pelvis after discussion with orthopaedics, and this showed bone marrow oedema of bilateral neck of femur, greater trochanter and right acetabulum. He was felt to have CRMO at this point and seen by paediatric rheumatology. His blood investigations showed mildly raised inflammatory markers with normal counts. His whole body MRI showed bone marrow oedema of T12-L2, in addition to above changes. His symptoms were cyclical lasting 3-4 weeks, often affecting ribs, back, right hip and thigh. It improved with regular anti-inflammatory agents but never completely went away. His inflammatory markers were creeping up with ESR 54 and CRP 37. His blood counts, vitamin D and bone profile were normal. Given his spinal lesions and ongoing symptoms, he was discussed at the radiology MDT and given bisphosphonate infusions. Hardly a month later, the pain resurfaced and was worse, he was fatigued and had night time pain, more over the chest and back. His blood investigations remained the same with raised inflammatory markers. He had further imaging both MRI spine and whole-body MRI. At this point, the greatest concern was malignancy. He was discussed with haematology and had a bone marrow biopsy that was normal. He had a pulse of IV methylprednisolone after discussions with oncology who felt strongly this wasn’t malignancy. This helped transiently for 2 months before things took a turn for the worse. Discussion A year after his first presentation, this boy was still symptomatic, fatigued, had lost weight, 3 kgs in 3 months, developed night sweats and looked pale. His inflammatory markers had never reached baseline throughout, and he had refrained from most physical activities. His blood investigations showed dropping Hb 106 , rising platelets 604, rising CRP 99 and ESR 87 with normal white cells. Our team felt strongly about malignancy and pushed for CT chest abdomen and pelvis as per oncology protocol. This revealed diffuse irregular dilatation of the aorta with aneurysmal dilatation of left proximal subclavian artery. This was suggestive of Takayasu’s arteritis. We discussed this patient at the national vasculitis consortium. He was pulsed with IV methylprednisolone with weaning oral steroids and had 5 cycles of cyclophosphamide. His symptoms improved, gained weight, and energy levels improved, and he went back to his activities. He was then commenced on methotrexate and anti TNF for maintenance and is doing well currently. It was important that we had kept questioning the diagnosis given that his symptoms and inflammatory markers never settled and pushed for further investigations to uncover his entire diagnosis. It is hard to say if his CRMO presented first with Takayasu’s as an association or his musculoskeletal symptoms were a veiled presentation of Takayasu’s arteritis. Key learning points Persistent systemic symptoms or inflammation in CRMO is unusual, look for alternative diagnosis especially malignancy and associations with CRMO including Inflammatory bowel disease and vasculitis. In any clinical scenario if despite treatment plans carried out, the patient is not improving back to baseline, or the family are concerned, reconsider the diagnosis. When reviewing patients with CRMO, keep in mind associations and ask specific history considering those as well as focussed examination, and investigations including faecal calprotectin, HLA B27, radiological imaging as needed. Role of multidisciplinary team discussions are invaluable including radiology, oncology and allied health professionals amongst others.

Neutrophilic dermatosis of the hands (NDH) is an uncommon inflammatory condition recognized as a localized variant of Sweet syndrome, seen in older adults with malignancy or systemic inflammatory disease. We present a rare case of NDH in a 23-year-old male in an unusual location, without the typical associated systemic illness or recent trauma. The patient presented with recurrent, painful erythematous nodules exclusively on the fingers and a violaceous bulla-like plaque on the volar surface of the left index finger. Laboratory tests showed leukocytosis with neutrophilia, elevated erythrocyte sedimentation rate, and normal C-reactive protein levels. Investigations for other underlying causes were unremarkable. Histopathologic examination was consistent with NDH. He was treated with dapsone 50 mg daily, with resolution in 3 weeks, and no recurrence was reported. This case expands the clinical spectrum of NDH. It highlights the importance of considering it in the differential diagnosis of painful hand lesions in younger patients, even in the absence of typical risk factors or systemic involvement.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are immune-mediated disorders characterized by chronic gastrointestinal inflammation and a broad spectrum of extraintestinal manifestations. Among these, dermatological manifestations significantly impact patients' quality of life (QoL), presenting as conditions linked to IBD itself or IBD-related medical therapy. This comprehensive review underscores the relationship between IBD and cutaneous manifestations, with particular emphasis on erythema nodosum, pyoderma gangrenosum, Sweet syndrome, and hidradenitis suppurativa, alongside autoimmune conditions like psoriasis and vitiligo. The influence of biologic therapies, including both paradoxical skin reactions mimicking extraintestinal manifestations and nonspecific rashes, is also discussed, with a focus on the pathophysiological mechanisms and therapeutic approaches. Emerging evidence highlights the bidirectional interplay of gut-skin axis, with shared genetic, microbial, and immune pathways. Special considerations, such as pregnancy-related dermatoses, are included to provide a holistic view of this complex relationship. Improved comprehension of these manifestations not only emphasizes the necessity for interdisciplinary care, but also informs tailored therapies to address systemic inflammation while minimizing dermatological complications. This update offers practical insights and emerging evidence to guide clinicians in optimizing patient outcomes.

Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is characterized by painful erythematous plaques or nodules with diffuse infiltration of mature neutrophils in the dermis. Most patients respond well to systemic corticosteroids, except for a few resistant cases. SS may be idiopathic or triggered by trauma, infection, drugs, and immune disorders. The exact pathogenesis, pathophysiology and precise treatment options beyond corticosteroids remain unclear. We applied anti-IL-36R monoclonal antibody, Spesolimab, to treat two SS patients and achieved favorable outcomes, however, the molecular mechanism is unproved. Here, we applied spatiotemporal transcriptomics at single-cell resolution and multiplex immunofluorescence on the skin lesion and blood samples from SS patients before, during, and after anti-IL-36R treatment. Releasing of neutrophil extracellular traps (NETs) was observed in the distinct NETosis neutrophil lineage infiltrating SS lesions, which secreted neutrophil elastase to splice full-length IL-36 proteins into their active forms, amplifying the inflammatory signal. From spatial view, the co-localized niches of heterogenous maturation neutrophils and IL36RN+ differentiated keratinocytes were found at the interface of the epidermis and dermis. The heterogenous maturation neutrophil activated IL-36 signaling was considered as rapid inflammatory response and was eliminated after treatment. Meanwhile, CD8+ T cells were also recruited and participated in the interferon signaling interacted with keratinocytes and neutrophils in the SS lesion, which was considered as delayed inflammatory response. Overall, a forward loop consisting of keratinocytes, heterogenous maturation neutrophils and CD8+ T cells was constructed to decipher the potential pathogenesis of SS, and IL-36 activated by neutrophil elastase released from heterogenous maturation neutrophils was one of the drivers of the loop. Moreover, IL-36 signaling was confirmed as a novel and effective treatment target for SS, which may be served as an alternative option for corticosteroid-resistant cases as well as patients with contraindications.

Sweet syndrome is a neutrophilic dermatosis characterised by fever and multifocal tender, erythematous plaques or papules, which may enlarge or coalesce to form plaques with an uneven mamillated surface. Necrotizing sweet syndrome (NSS) is a severe and locally aggressive variant that may resemble necrotizing soft tissue infection clinically. In contrast to necrotizing fasciitis where prompt surgical debridement and broad-spectrum antibiotics are the mainstay of treatment, necrotizing sweet syndrome responds to systemic corticosteroids and immuno-suppressants. Surgical interventions may in fact result in propagation of the disease due to the pathergy phenomenon.Herein we report a case of necrotizing sweet syndrome involving lower limbs mimicking necrotizing fasciitis where initial surgical interventions resulted in a threatened limb and therapeutic challenges. The patient responded to high dose systemic corticosteroids and immunosuppressants. This case highlights the importance of communication between the surgeon, dermatologist and pathologist for early diagnosis of necrotizing sweet syndrome to reduce morbidity.

BackgroundDrug-induced Sweet’s syndrome (DISS), a rare but serious adverse drug reaction characterized by acute febrile neutrophilic dermatosis, remains difficult to identify due to its low incidence and diverse drug triggers.MethodsDrugs associated with DISS were systematically identified and characterized using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS; Q1 2004–Q4 2024). Reports were analyzed for baseline characteristics, comorbidities, time-to-onset, drug class distributions, and polypharmacy patterns assessed through drug co-occurrence network analysis. Disproportionality analysis identified candidate drugs, which were refined using the least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression. The main analysis excluded malignancy- and/or immune-related indications, with two sensitivity analyses to assess robustness. A cross-database consistency assessment was conducted in VigiBase, supplemented by PubMed literature review and product label examination.ResultsA total of 2,018 DISS cases involving 342 drugs were identified. The median time to onset was 22 (interquartile range: 7–98) days, with 55.60% occurring within 30 days. Ninety drugs demonstrated positive disproportionality signals; a similar pattern was observed in the subset of reports submitted by medical doctors. Of these, 24 remained significant in the main model (area under the curve = 0.815, 95% confidence interval: 0.775–0.856), predominantly comprising antineoplastic and anti-infective agents. Sensitivity analyses produced comparable results. Cross-database assessment in VigiBase identified overlap for 10 signals, while literature review supported associations for 15 drugs and 9 were documented as associated with SS in the product labels.ConclusionThis study provides a comprehensive evaluation of drugs associated with DISS using real-world pharmacovigilance data. The results reveal both established and previously unrecognized drug triggers, offering important insights to support early detection, clinical management, and improved drug safety monitoring from statistical and clinical perspectives.

Premises: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a rare late-onset autoinflammatory syndrome caused by a mutation in the UBA1 gene. It primarily affects men over 50 with a presentation that mimics autoimmune disorders (Sweet's syndrome, polychondritis, vasculitis) associated with hematological disorders (cytopenias, MDS, thromboembolic events).Clinical Case Description: Male, 55 years old. May 2022: diagnosis of macrocytic anemia and thrombocytopenia. BOM performed with a diagnosis of low-risk multilineage MDS, normal karyotype, EPN clone absent, indication for follow-up. October 2022: onset of fever, skin rash, widespread arthralgia, and autoimmune hemolytic anemia. They ruled out infectious causes, autoimmune serology, total-body CT scans, and PET scans. Started steroid 1 mg/kg with benefit. February 2023: reappearance of fever, anemia, thrombocytopenia, extreme reticulocytosis, but a negative Coombs test. It was associated with the appearance of Libman-Sacks endocarditis. A new cycle of cortisone has been administered. April 2023 repeated bone marrow aspiration with confirmation of MDS diagnosis. Cyclosporine therapy was initiated, followed by rituximab, with benefit on symptoms and improvement in blood count. In the presence of a picture of dysimmunity and MDS, a genetic test for the UBA1 mutation was performed, which was found to be present. The patient has been started on an allogeneic bone marrow transplant pathway.Conclusions: VEXAS syndrome is a rare autoinflammatory syndrome that should be considered in cases of hematological damage and symptoms of systemic inflammation in the absence of active rheumatological disease.

Sweet syndrome (also known as acute febrile neutrophilic dermatosis) is a rare inflammatory skin disorder characterized by erythematous plaques with a dense dermal neutrophilic infiltrate. The first-line therapy remains oral corticosteroids, which suppresses inflammation nonspecifically. Although neutrophils are typically short-lived, how they persist in Sweet syndrome skin and contribute to disease pathogenesis remains unclear. Here, we identify a previously unrecognized population of antigen-presenting cell–like (APC-like) neutrophils expressing MHC class II genes that are uniquely present in Sweet syndrome skin but absent in healthy tissue and the circulation. Keratinocytes extended neutrophil lifespan 10-fold in coculture experiments and drove the emergence of an APC-like phenotype in approximately 30% of neutrophils, mirroring observations in patients’ lesions. Mechanistically, keratinocyte-derived serum amyloid A1 (SAA1) signals through the formyl peptide receptor 2 (FPR2) on neutrophils to promote their survival. These long-lived neutrophils actively orchestrate local immune responses by recruiting T cells and inducing cytokine production. Strikingly, dual blockade of SAA1/FPR2 signaling restores neutrophil turnover to baseline levels, with efficacy comparable to high-dose corticosteroids. These findings uncover a keratinocyte/neutrophil/T cell axis that sustains chronic inflammation in Sweet syndrome and highlight the SAA1/FPR2 pathway as a promising target for precision therapy.

Patient: Female, 86-year-oldFinal Diagnosis: Myelodysplastic syndrome • Sweet syndromeSymptoms: Fever • nodular erythematous rash • pancytopeniaClinical Procedure: —Specialty: Dermatology • HematologyObjective: Unusual clinical courseBackgroundSweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory skin condition often associated with hematologic malignancies such as myelodysplastic syndrome (MDS). Therapy-related MDS (tMDS) is a well-recognized subtype of myelodysplastic syndrome that arises due to exposure to chemotherapy or radiation therapy. Reports on SS in the context of tMDS are limited, with unclear clinical features.Case ReportAn 86-year-old woman with low-grade B-cell lymphoma, unclassifiable, achieved complete remission following bendamustine-rituximab therapy. She later developed cytomegalovirus viremia, persistent fever, and painful erythematous nodules. Histopathological examination of a skin biopsy confirmed SS. Corticosteroids and colchicine were initiated, leading to resolution of cutaneous symptoms. Despite clinical improvement, she developed progressive pancytopenia. Bone marrow evaluation revealed granulocytic dysplasia, including hypogranulation and pseudo-Pelger-Huët anomalies, with 1.5% ring sideroblasts and 3.2% blasts, consistent with MDS. Azacitidine was administered but proved ineffective in restoring hematopoiesis. The patient died due to an invasive Aspergillus brain abscess. Autopsy findings confirmed the absence of lymphoma recurrence. A literature review identified only 4 previously published cases of SS in tMDS, all of which occurred after the diagnosis of tMDS.ConclusionsThis case is notable in that SS preceded the diagnosis of MDS, contrasting with previous reports. Although a direct causal relationship cannot be established, this case underscores the diagnostic complexity of cutaneous and hematologic findings following chemotherapy. Furthermore, the absence of consensus on corticosteroid dosing and duration in immunocompromised hosts highlights the need to carefully balance therapeutic benefits against infection risk in SS associated with hematologic malignancies.

Paraneoplastic dermatoses as initial presentation of multiple myeloma A 70-year-old woman presents with painful annular, papular to edematous erythematous lesions on the chin, neck, chest, and upper back. A skin biopsy shows a dense neutrophilic infiltrate in the dermis, consistent with Sweet's syndrome. In the following weeks, the clinical picture evolves into erythema gyratum repens, a rare paraneoplastic entity. Biochemical analysis reveals inflammatory markers with elevated sedimentation rate and the presence of a monoclonal spike. Further hematological examination leads to the diagnosis of multiple myeloma with osteolytic bone lesions, preserved renal function and absence of hypercalcemia. Treatment with daratumumab, lenalidomide and dexamethasone is initiated. Two months after starting treatment, the patient presents with rapidly growing nodules on the scalp. A biopsy confirms the presence of plasmocytomas, an extramedullar manifestation of multiple myeloma, for which radiotherapy is initiated. This case illustrates how paraneoplastic phenomena, specifically Sweet’s syndrome and erythema gyratum repens, can lead to the diagnosis of an internal malignancy. Paraneoplastic dermatoses are rare, yet timely recognition is essential for detecting an underlying malignancy. This article summarizes the available literature on cutaneous paraneoplastic phenomena in multiple myeloma.

0162 Keratinocytes induce neutrophils to acquire antigen presentation capability in sweet syndrome

Introduction: The incidence of cancers is increasing over the past few decades. With the surge of cancer cases, the usage of cancer chemotherapy drugs has increased. These drugs cause a myriad of cutaneous adverse effects leading to decreased quality of life. Aim: To study the frequency of cutaneous adverse effects of cancer chemotherapy drugs. Materials and Methods: This cross-sectional study was conducted in the Department of Dermatology Government Royapettah Hospital, Chennai, Tamil Nadu, India, from October 2024-November 2024. In present study, all the patients under cancer chemotherapy drugs for various malignancies with cutaneous adverse effects were included. All the cutaneous adverse effects were noted with proper documentation. The results were statistically analysed and tabulated in terms of frequency and percentage. Results: A total of 70 patients were included in the study. Among the 70 patients, 32 (45.7%) were male and 38 (54.2%) were female. Among the patients, 6 (8.6%) were less than 40 years of age, 29 (41.4%) were between 40-49 years, 15 (21.4%) were between 50-59 years, 9 (12.9%) were between 60-69 years, 6 (8.6%) were between 70-79 years and 5 (7.1%) were between 80-89 years. Carcinoma (Ca) breast was the most common malignancy observed in 23 (32.8%) in our study followed by Ca lung in 11 (15.7%) and Chronic Myeloid Leukaemia (CML) in 6 (8.5%). Anagen effluvium was the most common adverse effect observed in 53 (75.7%) followed by xerosis in 48 (68.6%), acneiform eruptions in 17 (24.3%), hyperpigmentation involving the skin, mucosa and nail in 14 (20%) and sweet syndrome in 8 (11.4%). Conclusion: The knowledge of adverse effects of chemotherapy drugs can help in early recognition and treatment. This helps in increasing the patient’s compliance and thereby increasing the quality of life.

A Combination Regimen of Adalimumab and Methotrexate in a Challenging Case of Recalcitrant Gut and Cutaneous Sweet Syndrome