Disease name and synonyms
Introduction
Definition and diagnostic criteria
Classical Sweet's syndrome
Classicala | Drug-inducedb |
---|---|
(1) Abrupt onset of painful erythematous plaques or nodules | (A) Abrupt onset of painful erythematous plaques or nodules |
(2) Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis | (B) Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis |
(3) Pyrexia >38°C | (C) Pyrexia >38°C |
(4) Association with an underlying hematologic or visceral malignancy, inflammatory disease, or pregnancy, OR preceded by an upper respiratory or gastrointestinal infection or vaccination | (D) Temporal relationship between drug ingestion and clinical presentation, OR temporally-related recurrence after oral challenge |
(5) Excellent response to treatment with systemic corticosteroids or potassium iodide | (E) Temporally-related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids |
(6) Abnormal laboratory values at presentation (three of four): erythrocyte sedimentation rate >20 mm/hr; positive C-reactive protein; >8,000 leukocytes; >70% neutrophils |
Malignancy-associated Sweet's syndrome
Drug-induced Sweet's syndrome
Epidemiology
Clinical Form | ||||
---|---|---|---|---|
Characteristic | Classicala | Hematologic malignancya | Solid tumora | Drug-inducedb |
Epidemiology
| ||||
Women | 80 | 50 | 59 | 71 |
Prior upper respiratory tract infection | 75–90 | 16 | 20 | 21 |
Recurrencec | 30 | 69 | 41 | 67 |
Clinical symptoms
| ||||
Feverd | 80–90 | 88 | 79 | 100 |
Musculoskeletal involvement | 12–56 | 26 | 34 | 21 |
Ocular involvement | 17–72 | 7 | 15 | 21 |
Lesion location
| ||||
Upper extremities | 80 | 89 | 97 | 71 |
Head and neck | 50 | 63 | 52 | 43 |
Trunk and back | 30 | 42 | 33 | 50 |
Lower extremities | Infrequent | 49 | 48 | 36 |
Oral mucous membranes | 2 | 12 | 3 | 7 |
Laboratory findings
| ||||
Neutrophiliae | 80 | 47 | 60 | 38 |
Elevated erythrocyte sedimentation ratef | 90 | 100 | 95 | 100 |
Anemiag | Infrequent | 82 | 83 | 100 |
Abnormal platelet counth | Infrequent | 68 | 50 | 50 |
Abnormal renal functioni | 11–50 | 15 | 7 | 0 |
Drug-induced Sweet's syndrome
Antibiotics | Minocycline [110-112] |
Nitrofurantoin [113] | |
Norfloxacin [114] | |
Ofloxacin [115] | |
Quinupristin/dalfopristin [118] | |
Trimethoprim-sulfamethoxazole [11,13] | |
Antiepileptics | Carbemazepine [17] |
Diazepam [86] | |
Antihuman immunodeficiency virus drugs | Abacavir (synthetic carbocyclic nucleoside analogue) [69] |
Antihypertensives | Hydralazine [107] |
Antineoplastics | Bortezomib [d] [78-79] |
Imatinib mesylate [e] [108,109,401] | |
Lenalidomide [f] [426] | |
Antipsychotics | Clozapine [82] |
Antithyroid hormone synthesis drugs | Propylthiouracil [117] |
Colony stimulating factors | Granulocyte-colony stimulating factor [39,41,89-105,398] |
Granulocyte-macrophage-colony stimulating factor [105,106] | |
Pegfilgrastim [g] [116] | |
Contraceptives [83] | Levonorgestrel/ethinyl estradiol (Triphasil) [84] |
Levonorgestrel-releasing intrauterine system (Mirena) [85] | |
Diuretics | Furosemide [88] |
Nonsteroidal anti-inflammatory agents | Celecoxib [80] |
Diclofenac [87] | |
Retinoids | All-trans retinoic acid [70-77,417] |
13-cis-retinoic acid [81,404] |
Clinical description
Symptoms
Skin lesions
Extracutaneous manifestations
Bone | Acute sterile arthritis, arthralgias, focal aseptic osteitis, pigmented villonodular synovitis, sterile osteomyelitis (chronic recurrent multifocal osteomyelitis) [12,32,44,164,212-215]. |
Central nervous system | Acute benign encephalitis, aseptic meningitis, brain SPECT abnormalities, brain stem lesions, cerebrospinal fluid abnormalities, computerized axial tomography abnormalities, electroencephalogram abnormalities, encephalitis, Guillain-Barre syndrome, idiopathic hypertrophic cranial pachymeningitis, idiopathic progressive bilateral sensorineural hearing loss, magnetic resonance imaging abnormalities, neurologic symptoms, "neuro-Sweet disease", pareses of central origin, polyneuropathy, psychiatric symptoms [33,68,212-229,423]. |
Ears | Tender red nodules and pustules that coalesced to form plaques in the external auditory canal and the tympanic membrane [230]. |
Eyes | Blepharitis, conjunctival erythematous lesions with tissue biopsy showing neutrophilic inflammation, conjunctival hemorrhage, conjunctivitis, dacryoadenitis, episcleritis, glaucoma, iridocyclitis, iritis, limbal nodules, ocular congestion, periocular swelling, peripheral ulcerative keratitis, retinal vasculitis, scleritis, uveitis [12,20,26,88,101,185,202,214,229,231-239,421]. |
Kidneys | Mesangiocapillary glomerulonephritis, urinalysis abnormalities (hematuria and proteinuria) [16,17,25,26,73]. |
Intestines | Intestine with extensive and diffuse neutrophilic inflammation, neutrophilic ileal infiltrate, pancolitis (culture-negative) [36,203,240,241]. |
Liver | Hepatic portal triad with neutrophilic inflammation, hepatic serum enzyme abnormalities, hepatomegaly [12,16,17,20,25,26,212,224,242]. |
Heart | Aortic stenosis (segmental), aortitis (neutrophilic and segmental), cardiomegaly, coronary artery occlusion, heart failure, myocardial infiltration by neutrophils, vascular (aorta, bracheocephalic trunk and coronary arteries) dilatation [243-247]. |
Lung | Bronchi (main stem) with red-bordered pustules, bronchi with neutrophilic inflammation, pleural effusion showing abundant neutrophils without microorganisms, progressive pharyngeal mucosal infiltration and edema resulting in upper-airway obstruction, and chest roentgenogram abnormalities: corticosteroid-responsive culture-negative infiltratives, pulmonary tissue with neutrophilic inflammation [17,20,73,101,138,139,165,205,212,246-251,434]. |
Mouth | Aphthous-like superficial lesions (buccal mucosa, tongue), bullae and vesicles (hemorrhagic: labial and gingival mucosa), gingival hyperplasia, necrotizing ulcerative periodontitis, nodules (necrotic: labial mucosa), papules (macerated: palate and tongue), pustules (individual and grouped: palate and pharynx), swelling (tongue), ulcers (buccal mucosa and palate) [26,75,102,117,203,249,252-254]. |
Muscles | Magnetic resonance imaging (T1-weighted and T2-weighted) abnormalities: high signal intensities due to myositis and fasciitis, myalgias (in up to half of the patients with idiopathic Sweet's syndrome), myositis (neutrophilic), tendinitis, tenosynovitis [73,75,244,255-257]. |
Spleen | Splenomegaly [212]. |
Included diseases
Associated diseases
Cancer | Hematologic malignancies (most commonly acute myelogenous leukemia) and solid tumors (most commonly carcinomas of the genitourinary organs, breast, and gastrointestinal tract) [15] |
Infections [12,16,17,19,20,125,126,166,186,259] | Most commonly of the upper respiratory tract (streptococcosis) [16,17,20,186] and the gastrointestinal tract (salmonellosis [19,166] and yersiniosis [12]) |
Inflammatory bowel disease [260] | Crohn's disease [12,16,17,20,30,115,164,187,261-267,411] and ulcerative colitis [12,16-18,20,30,214,268,269] |
Medications | Most commonly granulocyte colony-stimulating factor [11,13,17,39,41,69-124,404,417] |
Pregnancy [12,16,30,270,271,410] |
Behcet's disease [272] |
Erythema nodosum [17,30,186,187,190,214,236,264,266,273-276,405,415] |
Relapsing polychondritis [5,20,195,277-280,409,425] |
Rheumatoid arthritis [12,16,20,231] |
Sarcoidosis [18,188,274,281-283,409,413] |
Thyroid disease: Grave's disease [117,284,285] and Hashimoto's thyroiditis [12,286] |
Alpha 1-antitrypsin deficiency [42] |
Anti-factor VIII inhibitor [287] |
Antiphospholipid syndrome [1] |
Aortitis (Takayasu's arteritis) [286,288] |
Aplastic anemia [39,99] |
Autoimmune disorders: autoimmune thrombocytopenic purpura [401], connective tissue disease (undifferentiated) [401], dermatomyositis [20], lupus erythematosus (subacute [289] and systemic [119,290,401]), pemphigus vulgaris [291] and Sjogren's syndrome [12,17,265,433] |
Bronchiolitis obliterans and organizing pneumonia [292-294] |
Chemical fertilizer [158] |
Chronic fatigue syndrome [295] |
Cirrhosis (cryptogenic) [30] |
Cholelithiasis [421] |
Common bile duct and intrahepatic duct stones [19] |
Congenital dyserythropoietic anemia [18] |
Congenital neutropenia (Kostmann's syndrome) [97] |
Cutis laxa (acquired, Marshall syndrome) [38,42,245,246] |
Dressler's syndrome (postmyocardial infarction syndrome) [17] |
Eosinophilic granuloma [19] |
Fanconi anemia [36,241] |
Glycogen storage disease (Type Ib) [41] |
Granuloma annulare [296] |
IgA nephropathy (Berger's disease) [97] |
Immunizing agent (BCG vaccination and flu) [17,297,298,419] |
Immunodeficiency diseases: chronic granulomatous disease [37,299,300], complement deficiency [30], human immunodeficiency virus infection [98,254,302], and primary T-cell immunodeficiency disease [43,303]) |
Infections: Anaplasma phagocytophilum [304], bartholinitis [17], bronchitis [17], Capnocytophaga canimorsus [305], chlamydia [306-308], cholangitis [19], cholecystitis [12], coccidioidomycosis [309], cytomegalovirus [1,310,311], Entamoeba histolytica [214], Epstein-Barr virus [1], Francisella tularensis [312], Helicobacter pylori [313], hepatitis (acute hepatitis B [314], autoimmune [251], cholestatic [30], chronic active [315], hepatitis C [161], and prior hepatitis A [1]), herpes simplex [316,317], herpes zoster [119], histoplasmosis [259], human immunodeficiency virus [98,254,302], leprosy [19], lymphadenitis (not otherwise specified [318,319] and subacute necrotizing [212,318]), mycobacteria (nontuberculous) [19,212,316,320-322,401], otitis media [12,17], pancreatitis [30], Pasteurella multocida bronchitis [323], Penicillium species [401], Pneumocystis carinii pneumonia [324], pyelonephritis [12], Salmonella (group D cervical lymphadenitis) [401], Staphylococcus aureus [44,326,431], Staphylococcus epidermidis (methicillin resistant) [407], subacute bacterial endocarditis [327], tonsillitis [12,17,19], toxoplasmosis [328], Trichophyton rubrum [418], tuberculosis [17,329,330], ureaplasmosis [331], urinary tract [17,20], and vulvovaginitis [12,20] |
Malabsorption [30] |
Mid-dermal elastolysis [332] |
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) [333] |
Postoperative (pneumonectomy) [334] |
Psoriasis vulgaris [16] |
Rhinosinusitis [335] |
SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteomyelitis) [424] |
Still's disease [336] |
Thermal injury [160] |
Transient acantholytic dermatosis (Grover's disease) [337] |
Ureter obstruction [338] |
Urticaria (chronic) [17] |
Urticaria pigmentosa [12] |
Welding burns [339] |
Associated neutrophilic dermatoses
Associated leukemia cutis
Pathological description
Etiology
Diagnostic methods
Lesional skin biopsy
Laboratory evaluation
Differential diagnosis
Clinical differential diagnosis
Cutaneous conditions | Acral erythema Drug eruptions Halogenoderma Rosacea fulminans |
Infectious and inflammatory disorders | Bacterial sepsis Cellulitis Erysipelas Herpes simplex virus Herpes zoster virus Leprosy Lymphangiitis Panniculitis Pyoderma gangrenosum Syphilis Systemic mycoses Thrombophlebitis Tuberculosis Viral exanthem |
Neoplastic conditions | Chloroma Leukemia cutis Lymphoma Metastatic tumor |
Reactive erythemas | Erythema multiforme Erythema nodosum Urticaria |
Systemic diseases | Behcet's disease Bowel bypass syndrome Dermatomyositis Familial Mediterranean fever Lupus erythematosus |
Vasculitis | Erythema elevatum diutinum Granuloma faciale Leukocytoclastic vasculitis Periarteritis nodosa |
Histologic differential diagnosis
Abscess/cellulitis | Positive culture for infectious agent |
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Bowel (intestinal) bypass syndrome | History of jejunal-ileal bypass surgery for morbid obesity |
Erythema elevatum diutinum | Erythematous asymptomatic plaques often located on the dorsal hands and elbows; younger lesions have microscopic features of leukocytoclastic vasculitis, whereas older lesions have dermal fibrosis and mucin |
Granuloma faciale | Yellow to red to brown indurated asymptomatic facial plaques; there is a grenz zone of normal papillary dermis beneath which there is a dense diffuse inflammatory infiltrate of predominantly neutrophils (with microscopic features of leukocytoclastic vasculitis) and frequently numerous eosinophils |
Halogenoderma | Neutrophilic dermal infiltrate with necrosis and pseudoepitheliomatous hyperplasia with intraepidermal abscesses; history of ingestion of bromides (leg lesions), iodides (facial lesions), or topical fluoride gel to teeth during tumor radiation therapy to face |
Leukemia cutis | Dermal infiltrate consists of immature neutrophils |
Leukocytoclastic vasculitis | Vessel wall destruction – extravasated erythrocytes, fibrinoid necrosis of vessel walls, karyorrhexis, and neutrophils in the vessel wall |
Lobular neutrophilic panniculitides | In addition to subcutaneous Sweet's syndrome, these include alpha 1-antitrypsin deficiency syndrome, factitial panniculitis (secondary to the presence of iatrogenic or self-induced foreign bodies), infectious panniculitis (secondary to either a bacterial, fungal, mycobacterial, or protozoan organism), pancreatic panniculitis, rheumatoid arthritis-associated panniculitis |
Neutrophilic eccrine hidradenitis | Neutrophils around eccrine glands, often in patients with acute myelogenous leukemia receiving induction chemotherapy |
Pyoderma gangrenosum | Painful ulcer with overhanging, undermined violaceous edges |
Rheumatoid neutrophilic dermatitis | History of rheumatoid arthritis, nodules, and plaques |
Sweet's syndrome | Acute onset, fever, neutrophilia, and painful plaques |
Management
Topical or intralesional corticosteroids
First-line systemic agents
Corticosteroids
| |
---|---|
Prednisone | 1 mg/kg/day (usually ranging from 30 mg to 60 mg) as a single oral morning dose. Within 4 to 6 weeks, taper dose to 10 mg/day; however, some patients may require 2 to 3 months of treatment or intravenous therapy [10,23,49,250] |
Methylprednisolone sodium succinate | Intravenously administered (up to 1000 mg per day) over 1 or more hours, daily for 3 to 5 days. This is followed by a tapering oral dose of corticosteroid or another immunosuppressant agent [70,184,223,240,359-361]. |
Potassium iodide
| Administered orally as 300 mg enteric-coated tablets, 3 times each day (for a daily dose of 900 mg) or as a saturated solution (1 gram/ml of water) of potassium iodide (SSKI, also referred to as Lugol's solution), beginning at a dose of 3 drops 3 times each day (9 drops/day = 450 mg per day) and increasing by 1 drop 3 times per day, typically to a final dose of 21 drops/day (1050 mg) to 30 drops/day (1500 mg) [17,20,23,143,198,361-363,368-374,397].a |
Colchicine
| Administered orally at a dose of 0.5 mg three times each day (for a daily dose of 1.5 mg) [20,30,281,284,329,360,371,373,375-377,410]. |
Corticosteroids
Potassium iodide
Colchicine
Second-line systemic agents
Indomethacin
| Administered at a oral daily dose of 150 mg for 7 days, and then 100 mg per day for 14 days [259,261,284,378]. |
Clofazimine
| Administered orally at a daily dose of 200 mg for 4 weeks, and then 100 mg per day for 4 weeks [12,296,379]. |
Cyclosporin
| As monotherapy or as a second-line agent (after failure of first-line therapy or as a corticosteroid-sparing agent) [12,30,231,294,380,381]. Initial oral daily dose ranged from 2 mg/kg/d [380] to 4 mg/kg/d [231] to 10 mg/kg/d [12,381]; in the latter patient, from the 11th day the dose was reduced by 2 mg/kg/d every 2 days and discontinued on day 21 [12,381]. |
Dapsone
| As either monotherapy or in combination therapy. Initial oral dose ranged from 100 mg per day to 200 mg per day; the latter dose was either administered as a single dose or divided into 2 equal doses [17,20,30,203,221,245,284,372,382-384,421]. |