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Actas Dermo-sifiliograficas Jun 2016Sweet syndrome is the most representative entity of febrile neutrophilic dermatoses. It typically presents in patients with pirexya, neutrophilia, painful tender... (Review)
Review
Sweet syndrome is the most representative entity of febrile neutrophilic dermatoses. It typically presents in patients with pirexya, neutrophilia, painful tender erytomatous papules, nodules and plaques often distributed asymmetrically. Frequent sites include the face, neck and upper extremities. Affected sites show a characteristical neutrophilic infiltrate in the upper dermis. Its etiology remains elucidated, but it seems that can be mediated by a hypersensitivity reaction in which cytokines, followed by infiltration of neutrophils, may be involved. Systemic corticosteroids are the first-line of treatment in most cases. We present a concise review of the pathogenesis, classification, diagnosis and treatment update of this entity.
Topics: Algorithms; Humans; Sweet Syndrome
PubMed: 26826881
DOI: 10.1016/j.ad.2015.12.001 -
American Journal of Clinical Dermatology May 2022Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous... (Review)
Review
Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous papules/plaques/pustules/nodules commonly appearing on the upper limbs, trunk, and head and neck; histologically, SS is characterized by dense neutrophilic infiltrate in the dermis. SS is accompanied by fever; an elevation of inflammatory markers (e.g., erythrocyte sedimentation rate, C reactive protein) in serum may also be observed. Although most cases of SS are idiopathic, SS also occurs in the setting of malignancy or following administration of an associated drug. SS has also been reported in association with pregnancy and a burgeoning list of infectious (most commonly upper respiratory tract infections) and inflammatory diseases; likewise, the litany of possible iatrogenic triggers has also grown. Over the past several years, a wider spectrum of SS presentation has been realized, with several reports highlighting novel clinical and histological variants. Corticosteroids continue to be efficacious first-line therapy for the majority of patients with SS, although novel steroid-sparing agents have been recently added to the therapeutic armamentarium against refractory SS. New mechanisms of SS induction have also been recognized, although the precise etiology of SS still remains elusive. Here, we catalogue the various clinical and histological presentations of SS, summarize recently reported disease associations and iatrogenic triggers, and review treatment options. We also attempt to frame the findings of this review in the context of established and emerging paradigms of SS pathogenesis.
Topics: Adrenal Cortex Hormones; Humans; Iatrogenic Disease; Neck; Skin; Sweet Syndrome
PubMed: 35157247
DOI: 10.1007/s40257-022-00673-4 -
The New England Journal of Medicine Dec 2020Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory...
BACKGROUND
Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders.
METHODS
We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9-edited zebrafish were used as an in vivo model to assess gene function.
RESULTS
We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet's syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation.
CONCLUSIONS
Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.).
Topics: Age of Onset; Aged; Aged, 80 and over; Autoimmune Diseases; Cytokines; Exome; Genetic Diseases, X-Linked; Genotype; Giant Cell Arteritis; Humans; Immunoblotting; Inflammation; Male; Middle Aged; Multiple Myeloma; Mutation, Missense; Myelodysplastic Syndromes; Polyarteritis Nodosa; Polychondritis, Relapsing; Sequence Analysis, DNA; Sweet Syndrome; Syndrome; Ubiquitin-Activating Enzymes
PubMed: 33108101
DOI: 10.1056/NEJMoa2026834 -
Annals of Hematology Nov 2018Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger... (Review)
Review
Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen. In general, ADs do not seem to confer worse survival, although certain ADs may be associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet syndrome). While steroids and immunosuppressive treatment (IST) remain the backbone of first-line treatment, increasing evidence suggests that MDS-specific therapy as hypomethylating agents, based on their immunomodulatory effect, may be effective in treating these complications and for sparing steroids.
Topics: Age Factors; Autoimmune Diseases; Disease-Free Survival; Humans; Immunosuppression Therapy; Myelodysplastic Syndromes; Risk Factors; Survival Rate
PubMed: 30091023
DOI: 10.1007/s00277-018-3472-9 -
Reumatologia Clinica Jan 2024VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene... (Review)
Review
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory syndrome characterized by somatic mutations in the UBA1 gene and is considered the prototype of hematoinflammatory diseases. Patients with VEXAS syndrome exhibit inflammatory and hematological manifestations that can lead to clinical diagnoses such as relapsing polychondritis, polyarteritis nodosa, Sweet syndrome, and myelodysplastic syndrome. Diagnosis requires bone marrow evaluation to identify cytoplasmic vacuoles in myeloid and erythroid precursors. However, genetic confirmation of mutations in UBA1 is necessary. Treatment is challenging and often involves glucocorticoids and immunosuppressants with variable responses. Hypomethylating agents and allogenic haemopoietic stem cell transplant are considered promising therapies. Prognosis is influenced by genetic and clinical factors. The aim of this review is to provide an overview of the pathogenesis, clinical presentation, treatment, and prognosis of VEXAS syndrome for the Latin American medical community.
Topics: Adult; Humans; Myelodysplastic Syndromes; Glucocorticoids; Immunosuppressive Agents; Mutation; Skin Diseases, Genetic
PubMed: 38160120
DOI: 10.1016/j.reumae.2023.12.004 -
Dermatologic Therapy Jan 2021Dysgeusia is the first recognized oral symptom of novel coronavirus disease (COVID-19). In this review article, we described oral lesions of COVID-19 patients. We... (Review)
Review
Dysgeusia is the first recognized oral symptom of novel coronavirus disease (COVID-19). In this review article, we described oral lesions of COVID-19 patients. We searched PubMed library and Google Scholar for published literature since December 2019 until September 2020. Finally, we selected 35 articles including case reports, case series and letters to editor. Oral manifestations included ulcer, erosion, bulla, vesicle, pustule, fissured or depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, hemorrhagic crust, necrosis, petechiae, swelling, erythema, and spontaneous bleeding. The most common sites of involvement in descending order were tongue (38%), labial mucosa (26%), and palate (22%). Suggested diagnoses of the lesions were aphthous stomatitis, herpetiform lesions, candidiasis, vasculitis, Kawasaki-like, EM-like, mucositis, drug eruption, necrotizing periodontal disease, angina bullosa-like, angular cheilitis, atypical Sweet syndrome, and Melkerson-Rosenthal syndrome. Oral lesions were symptomatic in 68% of the cases. Oral lesions were nearly equal in both genders (49% female and 51% male). Patients with older age and higher severity of COVID-19 disease had more widespread and sever oral lesions. Lack of oral hygiene, opportunistic infections, stress, immunosuppression, vasculitis, and hyper-inflammatory response secondary to COVID-19 are the most important predisposing factors for onset of oral lesions in COVID-19 patients.
Topics: COVID-19; Humans; Mouth Diseases; SARS-CoV-2
PubMed: 33236823
DOI: 10.1111/dth.14578 -
Orphanet Journal of Rare Diseases Jul 2007Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic... (Review)
Review
Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Several hundreds cases of Sweet's syndrome have been published. Sweet's syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis. The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient. Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS. The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic corticosteroids, there is a prompt response consisting of dramatic improvement of both the dermatosis-related symptoms and skin lesions. Topical application of high potency corticosteroids or intralesional corticosteroids may be efficacious for treating localized lesions. Other first-line oral systemic agents are potassium iodide and colchicine. Second-line oral systemic agents include indomethacin, clofazimine, cyclosporine, and dapsone. The symptoms and lesions of Sweet's syndrome may resolved spontaneously, without any therapeutic intervention; however, recurrence may follow either spontaneous remission or therapy-induced clinical resolution.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Sweet Syndrome
PubMed: 17655751
DOI: 10.1186/1750-1172-2-34 -
Archives of Pathology & Laboratory... Apr 2024Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome.... (Review)
Review
CONTEXT.—
Myelodysplasia cutis is an emerging concept in cutaneous neoplasia. Many of these cases were previously included under the umbrella of histiocytoid Sweet syndrome. However, with the advent of next-generation sequencing, cutaneous involvement by myelodysplastic syndrome is being increasingly recognized.
OBJECTIVE.—
To review histiocytoid Sweet syndrome and myelodysplasia cutis and discuss our current understanding of these entities. Additionally, to discuss how next-generation sequencing can be applied in the evaluation of cutaneous infiltrates of immature histiocytoid cells.
DATA SOURCES.—
The English-language literature from 2005 to 2023 on the topic of histiocytoid Sweet syndrome and myelodysplasia cutis was reviewed.
CONCLUSIONS.—
Biopsy specimens showing infiltrates of histiocytoid, immature myeloid cells may represent cutaneous involvement by myelodysplastic syndrome. Close clinical correlation is recommended in these cases. Recent studies suggest that next-generation sequencing is useful in separating myelodysplasia cutis from true histiocytoid Sweet syndrome. This distinction has important implications for patients.
Topics: Humans; Myelodysplastic Syndromes; Skin; Skin Neoplasms; Sweet Syndrome
PubMed: 37787422
DOI: 10.5858/arpa.2023-0132-RA -
Current Dermatology Reports 2022Neutrophilic dermatoses are defined by the presence of a sterile neutrophilic infiltrate on histopathology. This review focuses on the pathogenesis, epidemiology,... (Review)
Review
PURPOSE OF REVIEW
Neutrophilic dermatoses are defined by the presence of a sterile neutrophilic infiltrate on histopathology. This review focuses on the pathogenesis, epidemiology, clinicopathological features, diagnosis, and management of four disorders: Sweet syndrome, pyoderma gangrenosum, Behçet syndrome, and neutrophilic eccrine hidradenitis.
RECENT FINDINGS
Recent studies have provided insight into the complex pathogenesis of neutrophilic dermatoses. Evidence supports an intricate interplay of abnormal neutrophil function and inflammasome activation, malignant transformation into dermal infiltrating neutrophils, and genetic predisposition.
SUMMARY
Neutrophilic dermatoses have diverse cutaneous and extracutaneous manifestations and may be associated with significant morbidity and mortality. Common underlying associations include infectious, inflammatory, and neoplastic disorders, as well as drug reactions. Emerging diagnostic and therapeutic frameworks identify an expanding role for biologic and targeted anti-inflammatory therapies.
PubMed: 35310367
DOI: 10.1007/s13671-022-00355-8