• Three main clinical contexts:

1. 1. Classic/idiopathic (sometimes post-infectious or associated with IBD/pregnancy). Cohen 2007 , von den Driesch 1994

   2. Associated with malignancy (especially hematological; may be accompanied by cytopenias). Cohen 1988 , Bourke 1997

   3. Drug-induced (classically G-CSF* ; also ATRA** and others). Thompson 2007

• Pathophysiology: hypersensitivity/cytokine reaction with neutrophil recruitment; response to blockade of IL-1 It supports an inflammasome-IL-1 axis in refractory cases. Cohen 2007, Kluger 2011

*G-CSF: graulocite colony-stimulating factor, ** ATRA: all-trans retinoic acid

• Elementary injury
  • Papules, nodules, and plaques erythematous or violaceous, painful; aspect pseudovesicular (due to dermal edema). von den Driesch 1994, Cohen 2007
• Typical areas
  • Face/neck, upper limbs and trunk (frequent, although not exclusive pattern). von den Driesch 1994
• prototypical picture
  • Abrupt onset + fever/malaise ± arthralgia, with neutrophilia and/or elevated ESR/CRP. Cohen 2007, Fat 1995
• Extracutaneous findings (key to oculoplastics/internal medicine)
  • Eyepiece: conjunctivitis, episcleritis/scleritis, ulcerative peripheral keratitis, iritis/uveitis; also orbital/periorbital inflammation (may mimic orbital cellulitis). Gottlieb 2008
  • Neurological: "neuro-Sweet"(aseptic meningoencephalitis/CNS manifestations) with proposed criteria. Hisanaga 2005
• Evolution
  • Answer speed boat tour to systemic corticosteroids (sometimes within 24–48 h); may recur. Sweet 1964, Cohen 2002, Cohen 2007
• Important atypical forms
  • Subcutaneous (neutrophilic panniculitis): predominance in subcutaneous cellular tissue; relevant relationship with hematological malignancy; may be confused with erythema nodosum. Guhl 2008
  • Histiocytoid: infiltrate of cells with histiocytic appearance but MPO+ (immature granulocytes); relatively greater association with MDS in comparative series. Requena 2005, Ghoufi 2016
  • Variants that mimic necrotizing fasciitis: “neutrophilic dermatosis variants resembling necrotizing fasciitis” → risk of unnecessary debridement if mistaken for infection. sanchez 2019

• Cellulitis/erysipelas: similar pain and fever, but there is usually an infectious focus/portal of entry and a response to antibiotics; in Sweet's syndrome, the biopsy shows a sterile neutrophilic infiltrate and a response to steroids. Cohen 2007

• Leukocytoclastic vasculitis: palpable purpura, necrosis; histology with primary vasculitis (secondary vascular changes may be present in Sweet's disease). von den Driesch 1994

• Pyoderma gangrenosum: ulceration with an undermined border and pathergy; it may coexist within the spectrum of neutrophilic dermatoses. Cohen 2007

• Erythema nodosum: painful pretibial nodules; septal histology (subcutaneous sweetness = neutrophilic panniculitis). Guhl 2008

• Cutaneous leukemia/tumor infiltration: suspect if atypical lesions + cytopenias/blasts; in histiocytoid, use IHC (MPO/CD15) and hematological correlation. Requena 2005 , Cohen 1988

• Histological pattern
  • Neutrophilic dermatitis: dense neutrophilic infiltrate in the dermis (frequent papillary edema) with leukocytoclasia; typically without primary vasculitis. von den Driesch 1994, Cohen 2007
• Key findings
  • Classic: neutrophil-rich inflammatory infiltrate in the dermis; edema. Cohen 2007
  • Histiocytoid: “histiocytoid” cells but intensely positive MPO (immature granulocytes). Requena 2005
  • Subcutaneous: neutrophilic panniculitis (sometimes predominantly lobular). Guhl 2008
• Useful IHC/stains (depending on differential)
  • To rule out infection when there is clinical doubt: Gram, PAS/GMS, Ziehl-Neelsen (and cultivation if applicable). Cohen 2007
  • If histiocytoid/leukemia cutis is suspected: MPO, CD15, correlation with hematology; some cases require additional studies. Requena 2005, Ghoufi 2016
• molecular tests
  • They are not routine for "classic" Sweet; they are reserved for suspected hematological neoplasia or alternative diagnoses. Cohen 1988, Ghoufi 2016

• Infection (bacterial, fungal, mycobacterial): neutrophils + microorganisms/positive stains/cultures. Cohen 2007

• Primary leukocytoclastic vasculitis: fibrinoid damage and neutrophils around vessels as the primary event. von den Driesch 1994

• Cutaneous leukemia: blastic infiltrate; in histiocytoid leukemia, MPO+ may be confusing—correlate with clinical presentation/blood count. Requena 2005

• Basic initial (most patients):
  • Complete blood count with differential (look for neutrophilia or cytopenias). Fat 1995, Cohen 1988
  • PCR/ESR (inflammatory activity). Fat 1995
  • Liver/kidney function (before colchicine/dapsone/cyclosporine if contemplated). Cohen 2002
• If malignancy or histiocytoid/subcutaneous variant is suspected:
  • Peripheral smear ± hematological assessment; in histiocytoid, hematological evaluation and follow-up of counts are recommended. Cohen 1988, Ghoufi 2016
• If there is extracutaneous data:
  • Urgent ophthalmology If you experience eye pain, photophobia, or decreased vision. Gottlieb 2008
  • Neuroimaging/CSF if meningoencephalitic syndrome compatible with neuro-Sweet (according to criteria). Hisanaga 2005
• Biopsy
  • Recommended type
    • Punch 4–6 mm deep (include reticular dermis; add subcutaneous cellular tissue (if subcutaneous form is suspected). Guhl 2008, Cohen 2007
  • Key considerations
    • Choosing early injury and active (not just ulcerated/necrotic area). Cohen 2007
    • If the differential includes infection: take a sample for culture separately (sterile container) in addition to the piece in formalin. Cohen 2007
  • Contraindications
    • Not specific; apply clinical judgment (anticoagulation, anatomical site, etc.).
  • Fixing/Shipping
    • Histology: 10% formalin

• front line
  • Systemic corticosteroid (e.g., prednisone/prednisolone tapering): gold standard and usually gives a rapid response. Cohen 2002, Cohen 2007
  • Topical or intralesional (adjuvant or limited cases). Cohen 2002
• Alternatives (when steroids are risky or as a cost-saving measure)
  • Colchicine o potassium iodideOral options with reported rapid response. Cohen 2002,
  • Other options with clinical experience: indomethacin, dapsone, cyclosporine, clofazimine (select by comorbidities). Cohen 2002
  • Refractory: blocking IL-1 (anakinra) with marked responses in reports, useful as a proof of concept. Kluger 2011
• Care/monitoring (high performance)
  • Before dapsoneG6PD, hemolysis/methemoglobinemia, and serial blood counts (if used). (Practical guide within therapeutic review). Cohen 2002
  • Colchicine: Monitor for cytopenias, GI toxicity, and adjustments for renal/hepatic function and interactions. Cohen 2002
  • Potassium iodide: Monitor for GI intolerance, iodine levels, and thyroid function in prolonged/high-risk treatments. Horio 1980, Cohen 2002
• Contraindications (practical)
  • Steroids: caution in uncontrolled infection; prioritize ruling out sepsis/infectious necrosis if the clinical picture suggests it. Cohen 2007, sanchez 2019
  • Pregnancy: individualize (specific review during pregnancy). Glennon 2024

• Suspicion of underlying neoplasia : older age, male sex, cytopenias , severe/atypical lesions, histiocytoid or subcutaneous → hematological evaluation and follow-up. Cohen 1988 , Bourke 1997 , Ghoufi 2016 , Guhl 2008

• Painful red eye / photophobia / decreased vision : risk of keratitis/uveitis/scleritis → ophthalmological emergency. Gottlieb 2008

• A clinical picture that “resembles necrotizing fasciitis” (disproportionate pain, purplish plaques, fever, antibiotic resistance): consider neutrophilic variant type NF; avoid repeated debridement without confirming infection. Sanchez 2019

• Neurological symptoms (severe headache, confusion, neck stiffness): consider NeuroSweet and apply diagnostic criteria. Hisanaga 2005

• Painful , erythematous-violaceous , “pseudovesicular” plaques with a rapid response to steroids are highly suggestive (after excluding infection). von den Driesch 1994 , Cohen 2002

• Histiocytoid staining may appear as "something else" under H&E; MPO+ provides guidance. Requena 2005

• Sweet RD. AN ACUTE FEBRILE NEUTROPHILIC DERMATOSIS. Br J Dermatol. 1964; 76: 349-356. DOI:10.1111/j.1365-2133.1964.tb14541.x. PMID: 14201182.
  Brief summary: Foundational publication that describes the original clinical picture of acute febrile neutrophilic dermatosis, establishing the clinical phenotype and the entity that would later bear the eponym.
  Sweet 1964

• Your WP, Liu HN. Diagnostic criteria for Sweet's syndrome. Skin. 1986;37(3):167–174. DOI: Not available in PubMed. PMID: 3514153.
  Brief summary: It proposes major and minor criteria for a "defined" diagnosis, having a lasting influence on clinical-histological diagnostic standardization.
  On 1986

• von den Driesch P. Sweet's syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol.1994;31(4):535–556; quiz 557–560. DOI: 10.1016/S0190-9622(94)70215-2. PMID: 8089280.
  Brief summary: Classic review that systematizes clinical presentation (including pseudovesicular appearance), associations (including pregnancy) and diagnostic-therapeutic approach, with a broad view of extracutaneous manifestations.
  von den Driesch 1994

• Fett DL, Gibson LE, Su WP. Sweet's syndrome: systemic signs and symptoms and associated disorders. Mayo Clin Proc. 1995;70(3):234–240. DOI: 10.4065/70.3.234. PMID: 7861810.
  Brief summary: Institutional series (Mayo Clinic) that characterizes systemic signs, associated comorbidities and response to treatment, useful for estimating the “systemic burden” beyond the skin.
  Fat 1995

• Bourke JF, Keohane S, Long CC, et al. Sweet's syndrome and malignancy in the UK Br J Dermatol.1997;137(4):609–613. DOI: 10.1111/j.1365-2133.1997.tb03796.x. PMID: 9390341.
  Brief summary: It analyzes the Sweet-malignancy relationship in the United Kingdom, providing clinical data applicable to cancer screening decisions and risk profiling.
  Bourke 1997

• Cohen PR, Talpaz M, Kurzrock R. Malignancy-associated Sweet's syndrome: review of the world literature. J Clin Oncol. 1988;6(12):1887–1897. DOI: 10.1200/JCO.1988.6.12.1887. PMID: 3058878.
  Brief summary: Seminal review that consolidates the association with cancer (particularly hematological), describes clinical clues (e.g., cytopenias) and highlights that Sweet may precede or coincide with the oncological diagnosis.
  Cohen 1988

• Cohen PR, Kurzrock R. Sweet's syndrome: a review of current treatment options. Am J Clin Dermatol.2002;3(2):117–131. DOI: 10.2165 / 00128071-200203020-00005. PMID: 11893223.
  Brief summary: Practical therapeutic review: corticosteroids as standard, and alternatives (colchicine, potassium iodide, indomethacin, dapsone, cyclosporine), with clinical guidance for scenarios where steroid is limited.
  Cohen 2002

• Cohen PR. Sweet's syndrome—a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007; 2: 34. DOI: 10.1186/1750-1172-2-34. PMID: 17655751. PMCID: PMC1963326.
  Brief summary: Comprehensive review (with full text in PMC) that integrates subtypes (classic, malignancy, drugs), clinical presentation, pathology, extracutaneous manifestations, and recurrences; excellent as a framework reference.
  Cohen 2007

• Thompson DF, Montarella KE. Drug-induced Sweet's syndrome. Ann Pharmacother. 2007;41(5):802–811. DOI:10.1345/aph.1H563. PMID: 17426076.
  Brief summary: Systematic review focused on pharmacovigilance; discusses strength of association by drug (highlighting G-CSF/ATRA) and proposes a causality approach useful in practice.
  Thompson 2007

• Nofal A, Abdelmaksoud A, Amer H, et al. Sweet's syndrome: diagnostic criteria revisited. J Dtsch Dermatol Ges. 2017;15(11):1081–1088. DOI: 10.1111/ddg.13350. PMID: 28981179.
  Brief summary: Re-evaluate diagnostic criteria in the face of incomplete or atypical presentations, providing a modern framework for "non-textbook" cases.
  Nofal 2017

• Gottlieb CC, Mishra A, Belliveau D, et al. Ocular involvement in acute febrile neutrophilic dermatosis (Sweet syndrome): new cases and review of the literature. Surv Ophthalmol. 2008;53(3):219–226. DOI:10.1016/j.survophthal.2008.02.006. PMID: 18501268.
  Brief summary: Key review to recognize the broad ocular spectrum (from conjunctivitis to uveitis/scleritis and orbital involvement) and prioritize urgent referral when appropriate.
  Gottlieb 2008

• Hisanaga K, Iwasaki Y, Itoyama Y; Neuro-Sweet Disease Study Group. Neuro-Sweet disease: clinical manifestations and criteria for diagnosis. neurology. 2005;64(10):1756–1761. DOI:10.1212/01.WNL.0000161848.34159.B5. PMID: 15911805.
  Brief summary: It defines neuro-Sweet as an entity with CNS involvement and proposes diagnostic criteria, facilitating differentiation from other neuroinflammatory syndromes.
  Hisanaga 2005

• Sanchez IM, Lowenstein S, Johnson KA, et al. Clinical Features of Neutrophilic Dermatoses Variants Resembling Necrotizing Fasciitis. JAMA Dermatol. 2019;155(1):79–84. DOI: 10.1001/jamadermatol.2018.3890. PMID: 30383110. PMCID: PMC6439570.
  Brief summary: Multicenter study characterizing neutrophilic variants that mimic necrotizing fasciitis; essential to prevent aggressive surgery when the process is sterile inflammation.
  sanchez 2019

• Guhl G, García-Díez A. Subcutaneous sweet syndrome. Dermatol Clin. 2008;26(4):541–551, viii–ix. DOI:10.1016/j.det.2008.06.003. PMID: 18793988.
  Brief summary: Review of subcutaneous Sweet's disease within the spectrum of neutrophilic panniculitis, with emphasis on differentials (erythema nodosum) and association with hematological malignancy.
  Guhl 2008

• Requena L, Kutzner H, Palmedo G, et al. Histiocytoid Sweet syndrome: a dermal infiltration of immature neutrophilic granulocytes. Arch Dermatol. 2005;141(7):834–842. DOI: 10.1001/archderm.141.7.834. PMID:16027297.
  Brief summary: Key series that defines the histiocytoid subtype and demonstrates by IHC (MPO, CD15 and others) that “histiocytoid” cells correspond to immature granulocytes, with diagnostic and oncohematological implications.
  Requena 2005

• Ghoufi L, Ortonne N, Ingen-Housz-Oro S, et al. Histiocytoid Sweet Syndrome… A Comparative Series of 62 Patients. Medicine (Baltimore). 2016, 95 (15): e3033. DOI: 10.1097/MD.0000000000003033. PMID: 27082547. PMCID: PMC4839791.
  Brief summary: Extensive comparison of histiocytoid vs. classic histiocytoids shows a significant association with MDS and recommends hematological evaluation and follow-up of counts, providing practical evidence for “red flags”.
  Ghoufi 2016

• Horio T, Imamura S, Danno K, et al. Treatment of acute febrile neutrophilic dermatosis (Sweet's Syndrome) with potassium iodide. Dermatological. 1980;160(5):341–347. DOI: 10.1159/000250516. PMID: 7364144.
  Brief summary: It reports the usefulness of potassium iodide as a therapeutic alternative, relevant when steroids are contraindicated or a rapid response is sought with another route.
  Horio 1980

• Kluger N, Gil-Bistes D, Guillot B, Bessis D. Efficacy of… anakinra… in a case of refractory Sweet's syndrome.Dermatology. 2011;222(2):123–127. DOI: 10.1159/000326112. PMID: 21464561.
  Brief summary: Refractory case with marked response to anakinra; supports the role of IL-1/inflammasome and paves the way for targeted therapies in difficult neutrophilic dermatoses.
  Kluger 2011

• Glennon CM, Tan AJ, Prabhu M, Kroshinsky D. Sweet syndrome in pregnancy: A narrative review. International Journal of Gynaecology and Obstetrics. 2024;166(2):538–550. DOI: 10.1002/ijgo.15713. PMID: 38881204.
  Brief summary: Review focused on pregnancy: presentation, relevant differential diagnoses and therapeutic considerations/maternal-fetal safety, useful for multidisciplinary management.
  Glennon 2024