Current Opinion in Hematology:
MYELOID BIOLOGY: Edited by David C. Dale
Acute febrile neutrophilic dermatosis (Sweet's syndrome)
Anzalone, Charles L.a; Cohen, Philip R.b,c,d
bDepartment of Dermatology, University of Texas Medical School at Houston
cUniversity of Houston Health Center
dDepartment of Dermatology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Correspondence to Philip R. Cohen, MD, 10991 Twinleaf Court, San Diego, CA 92131, USA. E-mail: firstname.lastname@example.org
Purpose of review: To highlight the recent observations regarding not only research but also the clinical features and management of Sweet's syndrome.
Recent findings: Some of the new insights concerning Sweet's syndrome include: (1) bortezomib-induced Sweet's syndrome (some of which are the histiocytoid variant), (2) a rare extracutaneous manifestation of Sweet's syndrome with cardiovascular involvement including coronary artery occlusion, and (3) the possibility that photosensitivity may have a role in the pathogenesis of Sweet's syndrome.
Summary: Animal models of Sweet's syndrome and new associated medication have been observed. The definitive mechanism of pathogenesis still remains to be elucidated. Recent observations in paediatric patients suggest evaluation of dermatosis-related cardiac involvement in patients with post-Sweet's syndrome cutis laxa. Treatment advances include antitumour necrosis factor- alpha drugs; however, these medications have also been associated with inducing Sweet's syndrome. Nearly 50 years after the initial description of an acute febrile neutrophilic dermatosis by Dr Robert Douglas Sweet, the dermatosis remains a fascinating condition with regard to laboratory investigation, clinical manifestations and treatment.
Sweet's syndrome (acute febrile neutrophilic dermatosis) is characterized by pyrexia, mature neutrophils in the blood and the upper dermis, painful red skin lesions and response to corticosteroid treatment. The features of this dermatosis are reviewed in several current studies [1,2▪,3,4▪,5–8,9▪,10–12,13▪▪,14–30,31▪,32,33▪▪,34–48,49▪▪,50–58,59▪▪,60–62,63▪,64–87,88▪▪,89,90▪,91,92]. We briefly describe the salient aspects of Sweet's syndrome and summarize the more recent advances regarding ‘what's new’ in this condition.
Acute febrile neutrophilic dermatosis was originally described by Dr Robert Douglas Sweet in 1964. Originally known as Gomm–Button disease (in reference to the first two patients), the condition eventually acquired the established eponym ‘Sweet's syndrome’ .
The geographic distribution of Sweet's syndrome is worldwide with no racial predilection. The condition presents in three clinical settings: classic (or idiopathic) Sweet's syndrome, malignancy-associated Sweet's syndrome and drug-induced Sweet's syndrome; diagnostic criteria have been established for the former and the latter [2▪].
CAUSE AND PATHOGENESIS
The pathogenesis of Sweet's syndrome remains to be elucidated. The process may be multifactorial and many causes have been proposed. Sweet's syndrome may result from a hypersensitivity reaction to a bacterial, tumour or viral antigen. The accompanying fever and peripheral leukocytosis suggests a septic process. Circulating autoantibodies, cytokines, dermal dendrocytes, immune complexes, human leukocyte antigen serotypes and leukotactic mechanisms have all been postulated to have an etiologic role in the development of Sweet's syndrome symptoms [3,4▪].
WHAT IS NEW?
Animal models of Sweet's syndrome have been described: an alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 – originally found in a mouse with clinical and histopathological characteristics resembling Sweet's syndrome – appears to be involved in the pathogenesis of certain subsets of neutrophilic dermatoses, including Sweet's syndrome . A sterile neutrophilic dermatosis of the skin – similar to Sweet's syndrome – has been described in a female Dachschund; the condition responded rapidly to corticosteroid therapy . Lesions resembling Sweet's syndrome were also reported in a female standard poodle; subsequent examination also revealed extracutaneous involvement of the oesophagus, heart, lungs and tarsus (joint space and synovium) .
The immunoreactivity of several cytokines (interleukin-8, interleukin-17 and tumour necrosis factor-alpha), inflammatory cell markers (CD3, CD163 and myeloperoxidase), metalloproteinases (metalloproteinase-2 and metalloproteinase-9) and vascular endothelial growth factor has displayed significantly higher values in the lesional skin of patients with Sweet's syndrome than in the lesional skin of non-Sweet's syndrome individuals or patients with other neutrophilic dermatoses . The coexistence of Sweet's syndrome, Hashimoto thyroiditis and psoriasis in a 48-year-old white woman suggests a possible CD4+ T-cell dysfunction .
Sweet's syndrome has been reported in a 5-week-old Japanese girl with non-B54 types of human leukocyte antigen [9▪]. She is one of the youngest patients reported with Sweet's syndrome; this observation suggests the importance of genetic background in association with the dermatosis [9▪].
It has been postulated that photosensitivity may play a role in the pathogenesis of Sweet's syndrome, although the pathomechanism is unknown. One theory suggests an isomorphic Koebner reaction; another proposed mechanism associates ultraviolet-B radiation with neutrophil activation and epidermal production of tumour necrosis factor-alpha and interleukin-8 . Indeed, experimental induction of Sweet's syndrome has been elicited by phototesting . Also, photoactivate drug-associated Sweet's syndrome has been observed in a woman who was receiving trimethoprim-sulfamethoxazole .
Pertinent clinical findings of Sweet's syndrome include characteristic cutaneous lesions with accompanying patient history symptoms, as well as other related findings (extracutaneous manifestation and associated conditions).
Sweet's syndrome patients may appear dramatically ill. Fever is the most frequent symptom; the skin eruptions are also usually accompanied by leukocytosis. Arthralgia, general malaise, headache and myalgia are other symptoms associated with Sweet's syndrome .
What is new?
Sweet's syndrome and its systemic manifestations closely mimic familial Mediterranean fever. The clinical similarities suggest the possibility of either a common underlying mechanism or that both diseases represent a continuum of a reactive neutrophilic condition .
Sweet's syndrome skin lesions are typically tender, red to violaceous papules or nodules; they may be pseudovesicular in appearance. The lesions are often distributed asymmetrically; frequent sites include the face, neck and upper extremities (Figs 1–3) [13▪▪].
What is new?
A new variant of neutrophilic dermatosis, described as an ‘acute necrotizing Sweet's syndrome’, is characterized by the rapid onset of edematous, erythematous, warm cutaneous lesions with deep tissue neutrophilic infiltration and soft tissue necrosis in the absence of an infectious cause .
‘Neutrophilic dermatosis of the dorsal hands’ or ‘pustular vasculitis of the dorsal hands’ refers to Sweet's syndrome lesions located predominantly on the dorsal hands [15–17]. Neutrophilic dermatosis of the hands has been reported following influenza vaccination . Several other patients have also developed Sweet's syndrome (not limited to the hands) after vaccination, including Bacillus Calmette–Guérin vaccine, influenza vaccine, pneumovax vaccine and small pox vaccine .
Sweet's syndrome lesions have also been located on the area of postmastectomy lymphedema in breast cancer patients .
Wolff's isotopic response is a dermatological eponym used to describe the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. Several manifestions of Sweet's syndrome have presented in this manner: a 59-year-old woman with Sweet's syndrome triggered by scalding , a 56-year-old woman with localized Sweet's syndrome in an irradiated field  and a bullous variant of Sweet's syndrome on the side of the check and neck where a herpes zoster infection previously occurred in a 75-year-old man . A possible relationship between Sweet's syndrome and a henna tattoo has also been reported .
Related physical findings
Common related physical findings include extracutaneous manifestations, associated conditions, associated neutrophilic dermatoses and concurrent leukaemia cutis.
Sites of extracutaneous manifestations of Sweet's syndrome include bones, central nervous system, ears, eyes, kidneys, intestines, liver, heart, lung, mouth, muscles and spleen. Ocular involvement may present in the classic form of Sweet's syndrome. In patients with haematologic disorders, oral mucosal ulcers occur more frequently than in patients with classic Sweet's syndrome [13▪▪,25].
What is new?
Neuro-Sweet's disease is a rare occurrence that can affect regions of the central nervous system, causing a wide variety of neurological symptoms [26–28]. Neuro-Sweet's disease presenting with self-remitting and reversible parkinsonism has been described in a 72-year-old man . Optic nerve involvement of Sweet's syndrome with panuveitis was reported in a 49-year-old man . A 47-year-old Thai woman with underlying Sweet's syndrome demonstrated bilateral endogenous endophthalmitis with chorioretinitis arising from nontuberculous mycobacterial infection .
A 76-year-old man experienced Sweet's syndrome associated pulmonary involvement and systemic inflammatory response syndrome [31▪]. Infection-related systemic inflammatory response syndrome is referred to as sepsis; however, the patient's persistently negative cultures suggested that his systemic inflammatory response syndrome was caused by Sweet's syndrome [31▪].
Sweet's syndrome with panniculitis has been reported in a 45-year-old white woman ; in addition, Rochael et al.[33▪▪] reported findings of panniculitis in 80% of patients in which the hypodermis was affected. MRI findings of dermatosis-associated neutrophilic fasciitis and musculoskeletal involvement were reported in a 62-year-old man with Sweet's syndrome . Sweet's syndrome with spleen and lymph node involvement preceded by parvovirus B19 infection was described in a 45-year-old white woman . A rapid, profound loss of hearing was reported in a 65-year-old woman with a 10-year history of Sweet syndrome; 7 years prior, she had been diagnosed with bilateral, progressive sensorineural hearing loss after a severe exacerbation of Sweet's syndrome . A rare extracutaneous manifestation of Sweet's syndrome with cardiovascular involvement including coronary artery occlusion in a 43-year-old man was recently reported .
Cancers (Figs 1–3), such as haematologic malignancies (most commonly acute myelogenous leukaemia) and solid tumours (most commonly carcinomas of the genitourinary organs, breast, and gastrointestinal tract), infections of the upper respiratory tract (streptococcosis) and the gastrointestinal tract (salmonellosis and yersiniosis), inflammatory bowel disease (Crohn's disease and ulcerative colitis), medications (most commonly granulocyte colony-stimulating factor), pregnancy and vaccinations (BCG and influenza) are conditions that are ‘probably’ related to Sweet's syndrome related. Possibly associated conditions include Behcet's disease, erythema nodosum, relapsing polychondritis, rheumatoid arthritis, sarcoidosis and thyroid disease (Grave's disease and Hashimoto's thyroiditis). Sweet's syndrome has been described in patients with several other conditions such as aortitis (Takayasu's arteritis), aplastic anaemia, bronchiolitis obliterans and organizing pneumonia, chronic granulomatous disease, cutis laxa (acquired, Marshall syndrome), hepatitis C infection, HIV and Sjogren's syndrome. However, the validity of their association in Sweet's syndrome patients remains to be established [2▪,4▪].
What is new?
Recently, the following conditions have been postulated to be associated with Sweet's syndrome: coeliac disease , cervical cancer and tuberculosis , Chlamydophila pneumonia infection leading to tracheo-bronchial involvement , chronic recurrent multifocal osteomyelitis , Fanconi anaemia , kidney transplantation , leptospirosis , microscopic polyangitis , pemphigus vulgaris , sporotrichosis  and systemic lupus erythematosus . Further research is required to demonstrate the legitimacy of each condition's association with Sweet's syndrome.
Sweet's syndrome associated cardiovascular involvement in children has been reported several times in the literature [49▪▪]. Recently, Sweet's syndrome with postinflammatory elastolysis and takayasu arteritis was reported in a 22-month-old white boy [49▪▪]. Three patients, ages 17, 16 and 7 months, developed cardiovascular involvement due to elastolysis of the heart and aorta, which resulted in death in two patients .
Human leukocyte antigen analysis serves as an important differentiator between Sweet's syndrome and Behcet's disease; in Japan, the B54 marker is more frequently associated with Sweet's syndrome, whereas the B51 marker is significantly higher in Behcet's disease .
Associated neutrophilic dermatoses
An inflammatory infiltrate of mature polymorphonuclear leukocytes is the characteristic feature of neutrophilic dermatoses involving the skin and mucosa. Erythema elevatum diutinum, neutrophilic eccrine hidradenitis, pyoderma gangrenosum, subcorneal pustular dermatosis and vasculitis are neutrophilic dermatoses that have been associated – either concurrently or sequentially – with Sweet's syndrome [1,25].
Concurrent leukaemia cutis
In patients with haematologic disorders, Sweet's syndrome may present in three settings: as a paraneoplastic syndrome (underlying an unsuspected malignancy or recurrence of a previously-treated malignancy), as a drug-induced dermatosis or as a skin lesion of the dermatosis, which concurrently demonstrates leukaemia cutis [4▪,25].
Several laboratory findings are required to confirm a diagnosis of Sweet's syndrome.
Sweet's syndrome is characterized by a diffuse infiltrate of mature neutrophils located in the papillary and upper reticular dermis; oedema may also be present. Although Sweet's syndrome is not considered to be a primary leukocytoclastic vasculitis, ‘secondary’ leukocytoclastic vasculitis – in which vasculitis-like changes are observed as an epiphenomenon ‘secondary’ to extensive presence of vascular neutrophils – may be observed in the skin lesions of some patients with Sweet's syndrome. Alteration of the epidermis or neutrophilic infiltration of the adipose tissue can also be observed [33▪▪,52].
What is new?
The presence of eosinophils in Sweet's syndrome may range from rare to abundant and may be unrelated to the use of medication [33▪▪]. A dense neutrophil infiltrate is a characteristic feature of Sweet's syndrome; however, histopathologic discretion must be taken, as this presenting feature may be mimicked by arthropod bites .
’Histiocytoid’ Sweet's syndrome refers to an infiltrate of immature myeloid cells with a histiocytoid appearance, which may be misinterpreted as histiocytes. A case of histiocytoid Sweet's syndrome was reported with neutropenia; similarly, this rare histological variant was also reported in a patient with underlying Hodgkin's lymphoma [54,55]. Histiocytoid Sweet's syndrome has also been reported subcutaneously; a 71-year-old man with myelodysplastic syndrome and refractory anaemia presented with a monocytic-histiocytic appearing infiltrate . Drug-induced histiocytoid Sweet's syndrome in patients receiving bortezomib has also been repeatedly observed . Histiocytoid Sweet's syndrome may pathologically resemble myeloid leukaemia cutis; hence a myeloperoxidase stain can be utilized to differentiate between the microscopically similar appearing conditions .
Other laboratory tests
Peripheral leukocytosis with neutrophilia and an elevated erythrocyte sedimentation rate are the most consistent laboratory abnormalities of Sweet's syndrome. However, these findings may not always be present, such as in oncology patients with anaemia, neutropaenia and/or abnormal platelet counts. Therefore, a complete blood count with leukocyte differential and platelet count, evaluation of acute phase reactants, serum chemistries and a urinalysis should be performed [2▪].
Further testing, less commonly implemented, may be used to confirm extracutaneous manifestations and malignancy in patients with Sweet's syndrome.
Evaluation for extracutaneous manifestations
Evaluation of extracutaneous manifestations of Sweet's syndrome may require other laboratory tests. Central nervous system involvement in patients with Sweet's syndrome may show cerebrospinal fluid abnormalities or changes in the structure or function on brain studies. Kidney and liver involvement in patients with Sweet's syndrome may require urinalysis and hepatic serum enzyme evaluation. Pulmonary involvement in patients with Sweet's syndrome may demonstrate corticosteroid-responsive culture negative infiltrates and pleural effusion on chest roentgrams [4▪,13▪▪].
Newly diagnosed Sweet's syndrome in patients without a prior cancer may be the initial manifestation of a previously undiagnosed malignancy. Age-appropriate workup, as specified by the American Cancer Society, should be considered for the detection of cancer in asymptomatic persons. As the diagnosis of Sweet's syndrome has preceded the associated haematologic malignancy by as long as 11 years, it may be reasonable to repeat the complete blood count with leukocyte differential and platelet count every 6–12 months [4▪,13▪▪].
Clinical and histologic features are considered in generating a differential diagnosis in patients with possible Sweet's syndrome.
Clinical differential diagnosis
Sweet's syndrome skin and mucosal lesions may resemble that of other conditions (Table 1). Cutaneous conditions and systemic diseases, as well as infectious and inflammatory disorders, neoplastic conditions, reactive erythemas and vasculitis should be considered in the clinical differential diagnosis .
What is new?
In addition to familial Mediterranean fever, azathioprine hypersensitivity reaction [59▪▪], chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome  and gemcitabine-associated Sweet syndrome-like eruptions  are recently reported conditions to be considered in the differential diagnosis of Sweet's syndrome.
Histologic differential diagnosis
Conditions characterized by neutrophilic dermatosis or neutrophilic panniculitis should be considered in the histologic differential diagnosis of Sweet's syndrome (Table 1). Lesional tissue culture for bacteria, fungi and mycobacteria should be performed to rule out infection, as pathologic changes associated with Sweet's syndrome are similar to abscess or cellulitis [33▪▪,52]. Sweet's syndrome-like reaction due to arthropod bites may also be considered in the histopathologic differential diagnosis .
Sweet's syndrome skin lesions may become secondarily infected. Reappearance of the dermatosis may signify a recurrence of cancer in malignancy-associated Sweet's syndrome. Sweet's syndrome-associated systemic manifestions – such as inflammatory bowel disease, sarcoidosis and thyroid diseases – may require disease-specific treatment [4▪].
Prognosis and clinical course
In classic Sweet's syndrome, the lesions and symptoms may eventually resolve without therapeutic intervention; however, the lesions can persist for weeks to months. Successful management of the underlying cancer results in subsequent improvement of Sweet's syndrome; likewise, discontinuation of the associated medication in drug-induced Sweet syndrome will result in a spontaneous resolution of the condition. The duration of Sweet's syndrome is variable; indeed, Sweet's syndrome recurrence may occur not only in cancer patients – prompting evaluation for the return of their malignancy – but also in individuals with either idiopathic or disease-associated Sweet's syndrome [2▪,4▪].
Systemic corticosteroids – usually administered orally – are the treatment of choice for Sweet's syndrome. Topical or intralesional corticosteroids have proven to efficaciously treat localized Sweet's syndrome lesions. Intravenous methylprednisone delivered in daily pulses may be used to treat patients with refractory disease [62,63▪].
Colchicine and potassium iodide are also considered to be first-line systemic treatments for Sweet's syndrome. Clofazimine, cyclosporine, dapsone and indomethacin are second-line therapies for Sweet's syndrome. Isolated reports and small studies have also described other effective drugs to treat Sweet's syndrome: chlorambucil, cyclophosphamide, danazol, etretinate, hepatitis therapy, immunoglobulin, interferon-α and tumour necrosis factor antagonists (adalimumab, etanercept, infliximab and thalidomide) [62,63▪].
What is new?
Several new treatment options have been proposed as a therapeutic option for Sweet's syndrome. Intravenous immunoglogulin in conjunction with standard treatment may provide a possible therapeutic role in the treatment of Sweet's syndrome . Anakinra, an anti-interleukin-1 receptor antagonist, has shown promise in the treatment of refractory Sweet's syndrome .
Drugs implicated in development of Sweet's syndrome continue to be observed (Table 2). More recently, the following medications have been associated with the dermatosis: aceclofenac , antiretroviral therapy (efavirenz, lamivudine, lopinavir, ritonavir and stavudine) [33▪▪,67], azacitidine [68,69,70], azathioprine [59▪▪,71,72], benzylthiouracil , bortezomib [57,74–76], carbamazepine , chloroquine , ciprofloxacin , clindamycin , cobalt chrome alloy , cyclooxygenase-2 inhibitor , hydralazine [77,83], interleukin-2 therapy , mitoxantrone , oral contraceptives [33▪▪] orphenadrine citrate [33▪▪] and propylthiouracil . The first report of trimethoprim-sulfamthoxazole induced Sweet's syndrome in a child was described by Khaled et al.. Interestingly, some of the drugs used for the treatment of Sweet's syndrome have also been observed, though rarely, to elicit the condition. These drugs include the tumour necrosis factor inhibitors adalimumab [88▪▪,89], etanercept , infliximab [88▪▪,89] and lenalidomide [91,92].
Sweet's syndrome, initially described by Dr Robert Douglas Sweet nearly 50 years ago as an ‘acute febrile neutrophilic dermatosis’, remains a fascinating dermatological condition with regard to clinical manifestations, laboratory investigation and treatment.
There is no one to acknowledge. There are neither colleagues nor funding bodies nor grants nor sponsorship to acknowledge.
Conflicts of interest
There are no conflicts of interest with regard to this article.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
▪ of special interest
▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 68–70).
1. Cohen PR. Sweet's syndrome: a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007; 2:34.
2▪. Cohen P, Honigsmann H, Kurzrock R. Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D, Wolff K. Acute febrile neutrophilic dermatosis. Fitzpatrick's dermatology in general medicine 8th ed.New York:McGraw-Hill Professional; 2012. 362–371.
Acute febrile neutrophilic dermatosis (Sweet's syndrome) is defined by several distinct symptoms and findings: acute onset of fever, erythematous and tender cutaneous lesions typically revealing an upper dermal infiltrate of mature neutrophils and prompt improvement of symptoms after initiation of treatment with systemic corticosteroids.
3. Marzano AV, Cugno M, Trevisan V, et al. Inflammatory cells, cytokines and matrix metalloproteinases in amicrobial pustulosis of the folds and other neutrophilic dermatoses. Int J Immunopathol Pharmacol 2011; 24:451–460.
4▪. Wojcik AS, Nishimori FS, Santamaría JR. Sweet's syndrome: a study of 23 cases. An Bras Dermatol 2011; 86:265–271.
A study of 23 patients revealed similar findings to those found in the literature.
5. Nesterovitch AB, Gyorfy Z, Hoffman MD, et al. Am J Pathol 2011; 178:1434–1441.
6. Gains MJ, Morency A, Sauvé F, et al. Canine sterile neutrophilic dermatitis (resembling Sweet's syndrome) in a Dachshund. Can Vet J 2010; 51:1397–1399.
7. Johnson CS, May ER, Myers RK, Hostetter JM. Extracutaneous neutrophilic inflammation in a dog with lesions resembling Sweet's syndrome. Vet Dermatol 2009; 20:200–205.
8. Saeed M, Brown GE, Agarwal A, et al. Autoimmune clustering: sweet syndrome, Hashimoto thyroiditis, and psoriasis. J Clin Rheumatol 2011; 17:76–78.
9▪. Omoya K, Naiki Y, Kato Z, et al. Sweet's syndrome in a neonate with non-B54 types of human leukocyte antigen. World J Pediatr 2012; 8:181–184.
Analysis of the human leukocyte antigen bound peptides for patients with Sweet's syndrome constructive in realizing the molecular mechanisms of the condition.
10. Natkunarajah J, Gordon K, Chow J, et al. Photoaggravated Sweet's syndrome. Clin Exp Dermatol 2010; 35:18–19.
11. Meyer V, Schneider SW, Bonsmann G, Beissert S. Experimentally confirmed induction of Sweet's syndrome by phototesting. Acta Derm Venereol 2011; 91:720–721.
12. Oskay T, Anadolu R. Sweet's syndrome in familial Mediterranean fever: possible continuum of the neutrophilic reaction as a new cutaneous feature of FMF. J Cutan Pathol 2009; 36:901–905.
13▪▪. Gray PE, Bock V, Ziegler DS, Wargon O. Neonatal Sweet syndrome: a potential marker of serious systemic illness. Pediatrics 2012; 129:e1353–e1359.
A diagnosis of Sweet's syndrome as a neonate may symbolize a serious underlying disorder. Further diagnostic investigation may be considered.
14. Kroshinsky D, Alloo A, Rothschild B, et al
. Necrotizing Sweet syndrome: a new variant of neutrophilic dermatosis mimicking necrotizing fasciitis. J Am Acad Dermatol 2012 [Epub ahead of print].
15. Malik M, Perkins W, Leach I. Antineutrophil cytoplasmic antibody-positive neutrophilic dermatosis of the dorsal hands. Clin Exp Dermatol 2012 [Epub ahead of print].
16. Wang YS, Tan A. Neutrophilic dermatosis of the dorsal hands: an emerging entity. J Eur Acad Dermatol Venereol 2009; 23:451–452.
17. Cook E, Epstein R, Miller R. A rare case of idiopathic neutrophilic dermatosis of the hands. Dermatol Online J 2011; 17:11.
18. Wolf R, Barzilai A, Davidovici B. Neutrophilic dermatosis of the hands after influenza vaccination. Int J Dermatol 2009; 48:66–68.
19. Hali F, Sbai M, Benchikhi H, et al. Sweet's syndrome after H1N1 influenza vaccination. Ann Dermatol Venereol 2010; 137:740–741.
20. Gutiérrez-Paredes E, González-Rodríguez A, Molina-Gallardo I, Jordá-Cuevas E. Neutrophilic dermatosis on postmastectomy lymphedema. Actas Dermosifiliogr 2012; 103:649–651.
21. Phua YS, Al-Ani SA, She RB, de Chalain TM. Sweet's syndrome triggered by scalding: a case study and review of the literature. Burns 2010; 36:49–52.
22. Lee GY, Do MO, Kim SH, et al. Localized Sweet's syndrome in an irradiated field. Ann Dermatol 2009; 21:300–303.
23. Endo Y, Tanioka M, Tanizaki H, et al. Bullous variant of Sweet's syndrome after herpes zoster virus infection. Case Rep Dermatol 2011; 3:259–262.
24. Rosmaninho A, Machado S, Amorim I, et al. Henna tattoo and Sweet's syndrome: a possible relation. Eur J Dermatol 2009; 19:642–643.
25. Halpern J, Salim A. Pediatric sweet syndrome: case report and literature review. Pediatr Dermatol 2009; 26:452–457.
26. Maxwell G, Archibald N, Turnbull D. Neuro-Sweet's disease. Pract Neurol 2012; 12:126–130.
27. Shimizu Y, Watanabe T, Nakada M, et al. Neuro-Sweet disease mimicking recurrent anaplastic astrocytoma associated with therapy-related myelodysplastic syndrome: a case report. Clin Neurol Neurosurg 2012; 114:1049–1051.
28. Niwa F, Tokuda T, Kimura M, et al. Self-remitting and reversible parkinsonism associated with neuro-Sweet disease. Intern Med 2010; 49:1201–1204.
29. Lobo AM, Stacy R, Cestari D, et al. Optic nerve involvement with panuveitis in Sweet syndrome. Ocul Immunol Inflamm 2011; 19:167–170.
30. Sinawat S, Yospaiboon Y, Sinawat S. Bilateral endogenous endophthalmitis in disseminated NTM infection: a case report. J Med Assoc Thai 2011; 94:632–636.
31▪. Shugarman IL, Schmit JM, Sbicca JA, Wirk B. Easily missed extracutaneous manifestation of malignancy-associated Sweet's syndrome: systemic inflammatory response syndrome. J Clin Oncol 2011; 29:e702–e705.
Sweet's syndrome, although termed a neutrophilic dermatosis, can involve any organ in the body (most commonly the lungs); this patient had lung involvement and systemic inflammatory response due to Sweet's syndrome rather than infection.
32. Bassi E, Rosso R, Fiandrino G, De Filippi C. Sweet's syndrome with panniculitis. G Ital Dermatol Venereol 2012; 147:127–128.
33▪▪. Rochael MC, Pantaleão L, Vilar EA, et al. Sweet's syndrome: study of 73 cases, emphasizing histopathological findings. An Bras Dermatol 2011; 86:702–707.
The findings of this work are in agreement with previously published results in the literature. Microscopic findings reported that the presence of eosinphils was unrelated to the use of medication and ranged from rare to abundant in number. A fifth report of Sweet's syndrome and Hodgkin's disease was noted.
34. Gaeta M, Mileto A, Musumeci O, et al. MRI findings of neutrophilic fasciitis in a patient with acute febrile neutrophilic dermatosis (Sweet's syndrome). Skeletal Radiol 2011; 40:779–782.
35. Fortna RR, Toporcer M, Elder DE, Junkins-Hopkins JM. A case of sweet syndrome with spleen and lymph node involvement preceded by parvovirus B19 infection, and a review of the literature on extracutaneous sweet syndrome. Am J Dermatopathol 2010; 32:621–627.
36. Cheng S, da Cruz M. Sweet's disease and profound, bilateral, sensorineural hearing loss. J Laryngol Otol 2010; 124:105–107.
37. Acikel S, Sari M, Akdemir R. The relationship between acute coronary syndrome and inflammation: a case of acute myocardial infarction associated with coronary involvement of Sweet's syndrome. Blood Coagul Fibrinolysis 2010; 21:703–706.
38. Eubank KV, Nash J, Duvic M. Sweet syndrome associated with celiac disease. Am J Clin Dermatol 2009; 10:343–345.
39. Serirat O, Thaipisuttikul Y. Sweet's syndrome associated with Mycobacterium tuberculosis and cervical cancer: a case report. J Med Assoc Thai 2011; 94 (Suppl 2):S119–S122.
40. Tanimura K, Kita H, Kanemitsu Y, et al. Tracheo-bronchial involvement in Sweet syndrome. Thorax 2010; 65:1119–1120.
41. Tlougan BE, Podjasek JO, O’Haver J, et al. Chronic recurrent multifocal osteomyelitis (CRMO) and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with associated neutrophilic dermatoses: a report of seven cases and review of the literature. Pediatr Dermatol 2009; 26:497–505.
42. Giulino L, Guinan EC, Gillio AP, et al. Sweet syndrome in patients with Fanconi anaemia: association with extracutaneous manifestations and progression of haematological disease. Br J Haematol 2011; 154:278–281.
43. Osband AJ, Laskow DA, Mann RA, et al. Sweet syndrome after kidney transplantation. Transplant Proc 2009; 41:1954–1956.
44. George P. Two uncommon manifestations of leptospirosis: Sweet's syndrome and central nervous system vasculitis. Asian Pac J Trop Med 2011; 4:83–84.
45. Saussine A, Gueguen A, de Menthon M, et al
. Sweet syndrome revealing microscopic polyangiitis. Rheumatology (Oxford) 2012; 51:1916–1917.
46. O’Toole A, O’Malley M. Sweet syndrome and pemphigus vulgaris. J Cutan Med Surg 2012; 16:128–130.
47. Freitas DF, Valle AC, Cuzzi T, et al. Sweet syndrome associated with sporotrichosis. Br J Dermatol 2012; 166:212–213.
48. Tabache F, El Kartouti A, Abdelilah T, et al. Systemic lupus erythematosus revealed by Sweet syndrome. Joint Bone Spine 2011; 78:420–421.
49▪▪. Ma EH, Akikusa JD, Macgregor D, et al
. Sweet's syndrome with postinflammatory elastolysis and takayasu arteritis in a child: a case report and literature review. Pediatr Dermatol 2012; 29:645–650.
Complications of postinflammatory elastolysis, such as Takayasu arteritis, may be an associated condition with Sweet's syndrome. Further investigation is suggested to justify the validity of the association.
50. Timmer-DE Mik L, Broekhuijsen-VAN Henten DM, Oldhoff JM, et al. Acquired cutis laxa in childhood Sweet's syndrome. Pediatr Dermatol 2009; 26:358–360.
51. Takahama H, Kanbe T. Neutrophilic dermatosis of the dorsal hands: a case showing HLA B54, the marker of Sweet's syndrome. Int J Dermatol 2010; 49:1079–1080.
52. Abbas O, Kibbi AG, Rubeiz N. Sweet's syndrome: retrospective study of clinical and histologic features of 44 cases from a tertiary care center. Int J Dermatol 2010; 49:1244–1249.
53. Battistella M, Bourrat E, Fardet L, et al. Sweet-like reaction due to arthropod bites: a histopathologic pitfall. Am J Dermatopathol 2012; 34:442–445.
54. Liu CI, Hsiao CH, Wu JT, Tsai TF. Sweet syndrome with histiocytoid infiltrate and neutropenia: a rare combination. J Am Acad Dermatol 2009; 61:882–884.
55. Hünermund A, Wendel AM, Geissinger E, et al. Typically atypical: histiocytoid Sweet syndrome, associated with malignancy. J Dtsch Dermatol Ges 2011; 9:666–669.
56. Lin J, Zhang Q, Chen M. Subcutaneous histiocytoid Sweet's syndrome in a patient associated with myelodysplastic syndrome-refractory anemia. J Dermatol 2012; 39:99–101.
57. Murase JE, Wu JJ, Theate I, et al. Bortezomib-induced histiocytoid Sweet syndrome. J Am Acad Dermatol 2009; 60:496–497.
58. Valerón-Almazán P, Bastida J, Vilar J, et al. Utility of myeloperoxidase stain in the differential diagnosis of leukemia cutis vs. hystiocitoid Sweet syndrome. Dermatol Online J 2011; 17:11.
59▪▪. Bidinger JJ, Sky K, Battafarano DF, Henning JS. The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome. J Am Acad Dermatol 2011; 65:184–191.
Hypersensitivity to azathioprine is present in a wide clinical spectrum from local neutrophilic disease to systemic involvement. Skin findings may be an important early diagnostic finding leading to a diagnosis of azathioprine hypersensitivity.
60. Torrelo A, Patel S, Colmenero I, et al. Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome. J Am Acad Dermatol 2010; 62:489–495.
61. Martorell-Calatayud A, Requena C, Sanmartin O, et al. Gemcitabine-associated sweet syndrome-like eruption. J Am Acad Dermatol 2011; 65:1236–1238.
62. Cohen PR. Neutrophilic dermatoses: a review of current treatment options. Am J Clin Dermatol 2009; 10:301–312.
63▪. Schadt CR, Callen JP. Management of neutrophilic dermatoses. Dermatol Ther 2012; 25:158–172.
The management strategies for the neutrophilic dermatoses Sweet's syndrome and pyoderma gangrenosum are similar.
64. Gill HH, Leung AY, Trendell-Smith NJ, et al. Sweet syndrome due to myelodysplastic syndrome: possible therapeutic role of intravenous immunoglobulin in addition to standard treatment. Adv Hematol 2010; 2010:328316.
65. Kluger N, Gil-Bistes D, Guillot B, Bessis D. Efficacy of antiinterleukin-1 receptor antagonist anakinra (Kineret) in a case of refractory Sweet's syndrome. Dermatology 2011; 222:123–127.
66. Carvalho R, Fernandes C, Afonso A, Cardoso J. Drug-induced Sweet's syndrome by aceclofenac. Cutan Ocul Toxicol 2011; 30:315–316.
67. Haddow LJ, Lehloenya R, Mosam A, et al. Sweet syndrome: adverse drug reaction or novel manifestation of HIV-associated immune reconstitution inflammatory syndrome? J Am Acad Dermatol 2011; 65:e23–e25.
68. Trickett HB, Cumpston A, Craig M. Azacitidine-associated Sweet's syndrome. Am J Health Syst Pharm 2012; 69:869–871.
69. Tintle S, Patel V, Ruskin A, Halasz C. Azacitidine: a new medication associated with Sweet syndrome. J Am Acad Dermatol 2011; 64:e77–e79.
70. Pang A, Tan KB, Aw D, et al. A case of Sweet's syndrome due to 5-Azacytidine and vorinostat in a patient with NK/T cell lymphoma. Cutan Ocul Toxicol 2012; 31:64–66.
71. Flores Martín IM, López-Sáez MP, Brugaletta Matheus DC, et al. Azathioprine-induced Sweet's syndrome. J Investig Allergol Clin Immunol 2012; 22:66–67.
72. Kim MJ, Jang KT, Choe YH. Azathioprine hypersensitivity presenting as sweet syndrome in a child with ulcerative colitis. Indian Pediatr 2011; 48:969–971.
73. Frigui M, Masmoudi A, Kaddour N, et al. Neutrophilic dermatosis associated with antineutrophilic cytoplasmic antibodies (ANCA) after benzylthiouracil therapy. Ann Dermatol Venereol 2009; 136:422–426.
74. Thuillier D, Lenglet A, Chaby G, et al. Bortezomib-induced eruption: Sweet syndrome? Two case reports. Ann Dermatol Venereol 2009; 136:427–430.
75. Thomas M, Cavelier Balloy B, Andreoli A, et al. Bortezomib-induced neutrophilic dermatosis with CD30+ lymphocytic infiltration. Ann Dermatol Venereol 2009; 136:438–442.
76. Tanguy-Schmidt A, Avenel-Audran M, Croué A, et al. Bortezomib-induced acute neutrophilic dermatosis. Ann Dermatol Venereol 2009; 136:443–446.
77. Lund JJ, Stratman EJ, Jose D, et al. Drug-induced bullous sweet syndrome with multiple autoimmune features. Autoimmune Dis 2010; 2011:176749.
78. El Moutaoui L, Zouhair K, Benchikhi H. Sweet syndrome induced by chloroquine. Ann Dermatol Venereol 2009; 136:56–57.
79. Baybay H, Elhatimi A, Idrissi R, et al. Sweet's syndrome following oral ciprofloxacin therapy. Ann Dermatol Venereol 2011; 138:606–607.
80. Kandula S, Burke WS, Goldfarb JN. Clindamycin-induced Sweet syndrome. J Am Acad Dermatol 2010; 62:898–900.
81. Tortorici S, Buzzanca ML, Burruano F, Difalco P. Sweet's syndrome induced by removable partial denture using a CoCr alloy: case report. Minerva Stomatol 2010; 59:285–287.
82. Rosmaninho A, Lobo I, Selores M. Sweet's syndrome associated with the intake of a selective cyclooxygenase-2 (COX-2) inhibitor. Cutan Ocul Toxicol 2011; 30:298–301.
83. Cartee TV, Chen SC. Sweet syndrome associated with hydralazine-induced lupus erythematosus. Cutis 2012; 89:121–124.
84. Rondina A, Watson AC. Bullous Sweet's syndrome and pseudolymphoma precipitated by IL-2 therapy. Cutis 2010; 85:206–213.
85. Kümpfel T, Gerdes LA, Flaig M, et al. Drug-induced Sweet's syndrome after mitoxantrone therapy in a patient with multiple sclerosis. Mult Scler 2011; 17:495–497.
86. Chen YX, Zhang W, Chen XN, et al. Propylthiouracil-induced antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis versus primary ANCA-associated renal vasculitis: a comparative study. J Rheumatol 2012; 39:558–563.
87. Khaled A, Kharfi M, Fazaa B, et al. A first case of trimethoprim-sulfamethoxazole induced Sweet's syndrome in a child. Pediatr Dermatol 2009; 26:744–746.
88▪▪. Keidel S, McColl A, Edmonds S. Sweet's syndrome after adalimumab therapy for refractory relapsing polychondritis. BMJ Case Rep. 2011; 2011. pii:bcr1020114935.
Coexisting relapsing polychondritis and Sweet's syndrome are a rare, yet likely, true disease association. Antitumour necrosis factor-alpha, such as adalimumab, is a treatment option for both relapsing polychondritis and Sweet's syndrome; interestingly, the drug has been involved with several drug-induced studies of Sweet's syndrome.
89. Hawryluk EB, Linskey KR, Duncan LM, Nazarian RM. Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists. J Cutan Pathol 2012; 39:481–492.
90▪. Díaz-Corpas T, Mateu-Puchades A, Morales-Suárez-Varela MM, Castells-Rodellas A. Retrospective study of patients diagnosed with Sweet syndrome in the health area of a tertiary hospital in the autonomous community of Valencia. Actas Dermosifiliogr 2012; 103:233–237.
One patient's condition (of the 24 studied) was associated with the administration of infliximab.
91. Thieu KP, Rosenbach M, Xu X, Kist JM. Neutrophilic dermatosis complicating lenalidomide therapy. J Am Acad Dermatol 2009; 61:709–710.
92. Tageja N, Giorgadze T, Zonder J. Dermatological complications following initiation of lenalidomide in a patient with chronic lymphocytic leukaemia. Intern Med J 2011; 41:286–288.
acute; dermatosis; febrile; neutrophilic; Sweet's syndrome
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