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Sweet syndrome (acute febrile neutrophilic dermatosis): Pathogenesis, clinical manifestations, and diagnosis

Sweet syndrome (acute febrile neutrophilic dermatosis): Pathogenesis, clinical manifestations, and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Jun 29, 2022.

INTRODUCTION — Sweet syndrome (acute febrile neutrophilic dermatosis) is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, edematous, and erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur.

The epidemiology, clinical features, and diagnosis of Sweet syndrome will be discussed here. Information on the treatment and prognosis of Sweet syndrome and an overview of other neutrophilic dermatoses are available separately. (See "Sweet syndrome (acute febrile neutrophilic dermatosis): Management and prognosis" and "Neutrophilic dermatoses".)

CLASSIFICATION — Sweet syndrome was first described by Dr. Robert Douglas Sweet in 1964, who documented the development of an acute inflammatory skin eruption with fever and leukocytosis in eight women, several of whom had preceding upper respiratory or gastrointestinal infections [1]. Since then, Sweet syndrome has been observed in association with a broad range of disorders. As a result, some authors divide Sweet syndrome into three subtypes based upon etiology:

Classical Sweet syndrome

Malignancy-associated Sweet syndrome

Drug-induced Sweet syndrome

Classical Sweet syndrome — Classical Sweet syndrome (also referred to as idiopathic Sweet syndrome) constitutes the majority of cases of Sweet syndrome and is defined as Sweet syndrome that meets the established diagnostic criteria and is not associated with malignancy or drug exposure (table 1) [2]. Classical Sweet syndrome may occur in the setting of a variety of medical conditions. The conditions that are most frequently associated with classical Sweet syndrome are listed below [2-5]:

Infections (particularly upper respiratory tract and gastrointestinal infections; Sweet syndrome usually develops one to three weeks after infection [6])

Inflammatory bowel disease (Crohn disease and ulcerative colitis)

Pregnancy

Less frequent and less definitive associations exist with other infections (eg, human immunodeficiency virus [HIV], tuberculosis, chlamydia, viral hepatitis), primary immunodeficiencies, autoimmune conditions (eg, Behçet syndrome, relapsing polychondritis, rheumatoid arthritis, sarcoidosis, autoimmune thyroid disease, connective tissue disorders including systemic lupus erythematosus and dermatomyositis), and VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome [2,7]. Further studies are necessary to determine the strength of the relationships between Sweet syndrome and these diseases.

VEXAS syndrome is an autoinflammatory syndrome that has been described in adult males. Dermatologic manifestations are common and were documented in 126 of 141 patients with VEXAS syndrome (89 percent) identified in a 2022 review of the literature [8]. Sweet syndrome-like lesions (tender, erythematous or violaceous nodules) appear to be the most frequent cutaneous finding. Other dermatologic features include cartilaginous involvement with aural and nasal chondritis, cutaneous vasculitis, and periorbital angioedema [8]. (See "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome'.)

Malignancy-associated Sweet syndrome — Malignancy-associated Sweet syndrome accounts for a significant portion of cases of Sweet syndrome [9-12]. A 1993 review of several retrospective series found that 25 of 118 patients with Sweet syndrome (21 percent) had a hematologic or solid tumor malignancy [9]. In children, malignancy-associated Sweet syndrome appears to primarily occur in children over the age of three years [10]. Rare cases of malignancy-associated Sweet syndrome have been reported in infants [13,14].

Sweet syndrome may precede, follow, or appear concurrently with a malignancy [9,15-47]. In patients with previous histories of cancer, the development of Sweet syndrome may portend disease recurrence [2].

Sweet syndrome is more likely to occur in association with hematologic malignancies than solid tumor cancers [12,47-49]. In a 1998 review of 79 patients with malignancies and Sweet syndrome, 69 (87 percent) had hematologic malignancies and 12 had solid tumors (15 percent), including two patients who had both acute myelogenous leukemia (AML) and prostate cancer [50]. AML is the malignancy most frequently associated with Sweet syndrome. In the review, AML accounted for 42 percent of the hematologic malignancies and myeloproliferative disorders constituted the second most common category of malignancy (22 percent) [50]. Among solid tumors, carcinomas of the genitourinary organs, breast, and gastrointestinal tract are most frequently linked with Sweet syndrome [9,51].

Certain patient characteristics may be associated with increased risk for malignancy. Retrospective studies of patients with Sweet syndrome have found patients with older age, anemia, thrombocytopenia, leukopenia, and lack of arthralgias more likely to have malignancy-associated Sweet syndrome [47,49].

In addition, risk for malignancy may be elevated in patients with the histiocytoid or subcutaneous histologic variant of Sweet syndrome. In a retrospective study of 62 patients with a histopathologic diagnosis of Sweet syndrome, 12 of 22 patients (55 percent) with histiocytoid Sweet syndrome had an associated hematologic malignancy compared with 10 of 40 patients (25 percent) with classical Sweet syndrome [52]. Myelodysplastic syndrome was the most common malignancy in patients with histiocytoid Sweet syndrome, occurring in 32 percent of these patients compared with 3 percent of patients with classical Sweet syndrome. In a separate retrospective study in which 36 of 83 patients (44 percent) with Sweet syndrome had malignancy-associated disease, histiocytoid and subcutaneous histopathologies were associated with malignancy [49]. All 13 patients with one of these histologic variants had a concurrent malignancy. (See 'Pathology findings' below.)

Drug-induced Sweet syndrome — Multiple drugs may contribute to Sweet syndrome [48,53-69]. A list of drugs that have been associated with Sweet syndrome is provided in a table (table 2). Granulocyte-colony stimulating factor (G-CSF) is the most widely reported contributory medication [56].

The development of neutrophilic dermatoses as a consequence of checkpoint inhibitor immunotherapy, including Sweet syndrome secondary to ipilimumab therapy, has been reported [70]. A drug-induced increase in immunologic activity is thought to contribute. (See "Toxicities associated with immune checkpoint inhibitors", section on 'Dermatologic and mucosal toxicity'.)

Sweet syndrome usually develops approximately two weeks after drug exposure in patients who lack a prior history of exposure to the inciting drug [71]. Recurrence of the syndrome usually develops after re-exposure to the inciting drug [2].

EPIDEMIOLOGY — Although individuals between the ages of 30 and 60 most frequently develop classical Sweet syndrome, infants, children, and older adults may also be affected [2,7,10]. The age of onset tends to be older among patients with malignancy-associated Sweet syndrome. In a retrospective study of patients seen at a single academic center, the average age at diagnosis was 68 years among 27 patients with malignancy-associated Sweet syndrome compared with 51 years among 41 patients with classic Sweet syndrome [48]. The mean age for reported pediatric cases is slightly over five years [10].

The sex distribution varies with the subtype of Sweet syndrome and patient age. In classical Sweet syndrome, 80 percent of patients are women, whereas the proportion of women is lower in other clinical variants [2]. In Sweet syndrome associated with drugs, solid tumors, and hematologic malignancies, the percentage of patients who are women is estimated to be 70, 60, and 50 percent [2]. The female predominance in Sweet syndrome does not appear to apply to children. In a systematic review that included 66 reports of children with Sweet syndrome, the disorder was twice as likely to occur in males among children under the age of three [10]. In children over the age of three, the sex distribution was equal.

There is no obvious racial predilection in Sweet syndrome.

PATHOGENESIS — The pathogenesis of Sweet syndrome is not well understood. Factors theorized to contribute to the development of this disorder include hypersensitivity reactions, cytokine dysregulation, and genetic susceptibility:

Hypersensitivity reaction – An immune reaction to bacterial, viral, tumor, or other antigens could influence the development of Sweet syndrome through stimulating the production of cytokines that promote neutrophil activation and infiltration [72]. The positive response to systemic glucocorticoids and reports of improvement in Sweet syndrome following treatment of bacterial infections or malignancies offer some support to this theory [72-74].

Cytokine dysregulation – Certain cytokines and chemokines may contribute to the initiation and propagation of the inflammatory response in Sweet syndrome. A role for granulocyte colony-stimulating factor (G-CSF) is compelling, since G-CSF increases circulating neutrophils and exogenous G-CSF is a common cause of drug-induced Sweet syndrome [56]. Moreover, higher serum levels of G-CSF have been detected in patients with active Sweet syndrome than in patients with inactive disease [75]. Increased production of G-CSF by tumor cells has also been proposed as a potential factor in malignancy-associated disease [2,76].

Other cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukins (eg, IL-1, IL-3, IL-6, and IL-8) are postulated to play roles in Sweet syndrome [77-80]. In a study of eight patients with Sweet syndrome, serum levels of Th1 cytokines, including IL-1 alpha, IL-1 beta, IL-2, and interferon-gamma were elevated, whereas levels of IL-4, a Th2 cytokine remained normal [81].

Genetic susceptibility – Abnormalities in chromosome 3q have been reported in association with Sweet syndrome in a few patients [33,82-84]. HLA-B54 has been linked to Sweet syndrome in Japanese patients [85,86]. In addition, mutations in the MEFV gene, a gene associated with familial Mediterranean fever, have been detected in two patients with myelodysplastic syndrome and cutaneous findings consistent with Sweet syndrome [87].

Antibodies to neutrophilic cytoplasmic antigens have been detected in some patients with Sweet syndrome [84,88]. However, a pathogenic role for these antibodies has not been established. Further study is necessary to clarify the mechanisms that lead to the development of Sweet syndrome.

CLINICAL MANIFESTATIONS — In addition to the abrupt onset of the painful inflammatory papules, plaques, and nodules that characterize Sweet syndrome, additional clinical features may develop. An overview of the mucocutaneous and extracutaneous manifestations of Sweet syndrome is provided below. The differences in the clinical and laboratory features of the subtypes of Sweet syndrome are provided in a table (table 3).

Cutaneous — The cutaneous lesions of Sweet syndrome typically present as tender, edematous, and inflamed papules, plaques, and nodules (picture 1A-F). Lesions are usually several millimeters to several centimeters in diameter and exhibit a brightly erythematous or violaceous color.

The inflammatory papules and plaques often exhibit a mamillated surface [89]. Significant superficial dermal edema leading to a pseudovesicular quality is common. Pustules may also be present. In some cases, the skin lesions develop a central yellowish hue resulting in a targetoid appearance.

The distribution of the cutaneous eruption is often asymmetrical. The upper extremities appear to be the most common site of involvement [2,48]. Lesions also frequently develop on the trunk, lower extremities, head, and neck [48].

Patients often describe the pain associated with cutaneous lesions in Sweet syndrome as tenderness or a burning sensation. Although our experience suggests that pruritus rarely occurs, a retrospective study of 77 patients with Sweet syndrome found documentation of pruritus in 18 percent of patients [48].

Less common presentations of Sweet syndrome include:

Bullous Sweet syndrome – Bullous Sweet syndrome is an uncommon presentation of Sweet syndrome in which vesicles and flaccid bullae overly erythematous to violaceous plaques (picture 2A-B) [72]. Ulceration resembling pyoderma gangrenosum may occur in bullous Sweet syndrome; this manifestation most commonly occurs in the setting of hematologic malignancy [12,30,89].

Subcutaneous Sweet syndrome – In subcutaneous Sweet syndrome, the site of neutrophilic infiltration is in the subcutaneous fat, rather than the dermis (see 'Pathology findings' below). This results in the development of erythematous nodules with minimal superficial change. The nodules are usually 2 to 3 cm in diameter [90], and the extremities are common sites of involvement. Subcutaneous Sweet syndrome can closely resemble erythema nodosum, particularly when it involves the lower legs (picture 3) [91].

Neutrophilic dermatosis of the dorsal hands – Neutrophilic dermatosis of the dorsal hands (also known as pustular vasculitis of the dorsal hands) is a localized disorder that may be on a continuum with Sweet syndrome [92]. Affected patients develop inflammatory and pustular plaques on the dorsal surfaces of the hands (picture 4). Neutrophilic dermatosis of the dorsal hands is discussed in greater detail separately. (See "Neutrophilic dermatoses", section on 'Neutrophilic dermatosis of the dorsal hands'.)

In addition, patients with Sweet syndrome resembling necrotizing fasciitis (necrotizing Sweet syndrome) have been reported [93,94]. Patients present with fever accompanied by expanding erythematous to violaceous plaques. Underlying risk factors for Sweet syndrome (exposure to G-CSF, malignancy, and/or HIV infection) may be present. (See "Neutrophilic dermatoses", section on 'Necrotizing neutrophilic dermatoses' and "Necrotizing soft tissue infections", section on 'Necrotizing fasciitis'.)

Large cellulitis-like plaques may be another rare clinical presentation of Sweet syndrome. The term "giant cellulitis-like Sweet syndrome" was used to refer to the development of large infiltrated inflammatory plaques and bullae in three patients who met diagnostic criteria for Sweet syndrome [95]. (See 'Diagnostic criteria' below.)

The phenomenon of pathergy (lesion development at sites of cutaneous injury) may occur in patients with Sweet syndrome [10]. Even minor trauma, such as that obtained with a needle stick, may result in the development of skin lesions.

Oral cavity — Oral involvement is uncommon in classical Sweet syndrome. However, approximately 12 percent of patients with Sweet syndrome related to hematologic malignancies develop oral ulcers as a disease manifestation, particularly on the buccal mucosa or tongue (table 3) [2]. Additional reported oral findings include bullae, vesicles, gingival hyperplasia, necrotizing ulcerative periodontitis, nodules, papules, pustules, and tongue swelling [2,96].

Associated symptoms — The name "acute febrile neutrophilic dermatosis" reflects the frequent presence of fever >38°C in Sweet syndrome. Patients with drug-induced Sweet syndrome are almost always febrile, but fever may spare 10 to 20 percent of patients with classical or malignancy-associated disease (table 3) [2]. Arthralgias, malaise, headache, and myalgias are additional symptoms that frequently occur in Sweet syndrome [6,89].

Extracutaneous disease — Neutrophilic infiltration of other organ systems, such as the eye, muscles, lung, bone, liver, spleen, heart, kidneys, central nervous system, and gastrointestinal system may occur in Sweet syndrome, resulting in signs or symptoms specific to the extracutaneous site of inflammation. Ocular inflammation is a common extracutaneous manifestation; ocular involvement occurs in 17 to 72 percent of patients with the classical variant [2]. Examples of ocular manifestations include conjunctivitis, episcleritis, scleritis, limbal nodules, peripheral ulcerative keratitis, iritis, glaucoma, dacryoadenitis, and choroiditis [97,98]. The musculoskeletal system is another frequent site of extracutaneous involvement, manifesting as arthralgias, arthritis, and myalgias.

Examples of uncommon extracutaneous manifestations of Sweet syndrome include [6,89]:

Central nervous system – Encephalitis, aseptic meningitis

Cardiovascular system – Myocarditis, aortitis and aortic stenosis, coronary artery occlusion

Pulmonary system – Neutrophilic alveolitis, pleural effusions, airway obstruction

Liver – Hepatitis, hepatomegaly

Intestines – Neutrophilic inflammation of intestines

Spleen – Splenomegaly

Kidneys – Mesangial glomerulonephritis, hematuria, proteinuria

Bone – Sterile osteomyelitis

The development of systemic inflammatory response syndrome (SIRS) in the setting of Sweet syndrome has also been reported [18,99-101].

Associated laboratory findings — Peripheral leukocytosis with neutrophilia is the most common laboratory abnormality in patients with Sweet syndrome. Neutrophilia is present in the vast majority of patients with classical Sweet syndrome, and in a significant proportion of patients with malignancy-associated and drug-induced disease (table 3). Nonspecific inflammatory markers such as the erythrocyte sedimentation rate and C-reactive protein level are also frequently elevated in patients with Sweet syndrome.

Anemia and platelet abnormalities are commonly seen in Sweet syndrome related to malignancy or drugs, but are infrequently detected in patients with classical Sweet syndrome (table 3) [2,48]. Abnormalities on the complete metabolic panel and urinalysis may indicate hepatic or renal involvement.

DIAGNOSIS — The diagnosis of Sweet syndrome is based upon the recognition of consistent clinical and laboratory findings as well as the exclusion of disorders that may present with similar clinical features. A rapid and dramatic response to systemic glucocorticoid therapy also supports the diagnosis.

Diagnostic criteria — A revised set of diagnostic criteria [102] based upon criteria outlined in 1986 [54] is widely used for the diagnosis of Sweet syndrome (table 1). Both major criteria and two of four minor criteria are required to establish a diagnosis of classical or malignancy-associated Sweet syndrome:

Major criteria:

Abrupt onset of painful erythematous plaques or nodules

Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis

Minor criteria:

Pyrexia >38°C

Association with underlying hematologic or visceral malignancy, inflammatory disease or pregnancy, or preceded by upper respiratory infection, gastrointestinal infection, or vaccination

Excellent response to treatment with systemic glucocorticoids or potassium iodide

Abnormal laboratory values at presentation (three of four of the following: erythrocyte sedimentation rate >20 mm/hour, positive C-reactive protein, >8000 leukocytes, >70 percent neutrophils)

A separate set of criteria has been proposed for drug-induced Sweet syndrome (table 1) [53].

Clinical assessment — The clinical assessment of the patient offers valuable clues for diagnosis. The history may reveal a rapid onset of skin lesions and the presence of associated symptoms (eg, painful skin lesions, fever, malaise), findings that are compatible with Sweet syndrome. In addition, the knowledge that a patient has a condition known to occur in association with Sweet syndrome (eg, recent infection, malignancy, pregnancy, or inflammatory bowel disease) raises clinical suspicion for the diagnosis. (See 'Clinical manifestations' above and 'Classification' above.)

A complete physical examination that includes surveillance of the entire skin surface should be performed. This aids in determining whether the morphology and distribution of skin lesions is consistent with Sweet syndrome and allows for an assessment of the extent of cutaneous disease as well as an evaluation for signs of extracutaneous involvement.

Laboratory studies — In patients in whom the clinical findings suggest the possibility of Sweet syndrome, a skin biopsy and select laboratory tests are indicated.

Biopsy — The detection of consistent histologic findings is a major diagnostic criterion for Sweet syndrome (table 1) (see 'Diagnostic criteria' above). Thus, a skin biopsy should be performed whenever feasible.

Procedure — In patients with inflammatory papules or plaques, a 4 mm punch biopsy is usually sufficient for obtaining a tissue specimen for histologic examination. Because infection may closely resemble Sweet syndrome, microbial pathology stains should be performed. In addition, we obtain a second 4 mm punch biopsy for bacterial, fungal, and mycobacterial cultures. If pustules are present, a swab specimen can also be sent for culture.

In patients with nodules suggestive of subcutaneous Sweet syndrome (a variant in which the pathologic process is primarily located in the subcutaneous fat), an excisional biopsy is preferred because it provides a more generous sample of the subcutaneous fat, which may facilitate the interpretation of the histologic findings. As above, a portion of the tissue specimen should be sent for microbial cultures. (See 'Pathology findings' below and "Skin biopsy techniques" and "Panniculitis: Recognition and diagnosis", section on 'Biopsy'.)

Pathology findings — The characteristic histologic features of Sweet syndrome include [103]:

Prominent edema in the superficial dermis

Dense infiltrate of neutrophils in the upper and mid-dermis with sparing of the epidermis (picture 5)

Leukocytoclasis

Endothelial swelling

Absence of vasculitis (see below)

A few eosinophils may also be present. Older lesions may exhibit small numbers of lymphocytes or macrophages [103].

Although the absence of vasculitis is considered a characteristic feature of Sweet syndrome, the identification of vasculitis in a biopsy specimen does not rule out the diagnosis. In a retrospective study of skin biopsies from 21 patients with Sweet syndrome, vasculitis was identified in specimens from 6 patients (29 percent) [104]. The vasculitis seen in Sweet syndrome may be a secondary phenomenon related to the release of noxious products from neutrophils [104].

Pathologic variants of Sweet syndrome include subcutaneous Sweet syndrome and histiocytoid Sweet syndrome [105-110]. Subcutaneous Sweet syndrome is characterized by a dense neutrophilic infiltrate in the subcutaneous tissue. Although lobular inflammation is usually most prominent, both septa and lobules may be involved [90]. In histiocytoid Sweet syndrome, the dermal inflammatory infiltrate is primarily composed of histiocyte-like immature myeloid cells [111]. Histiocytoid Sweet syndrome may be difficult to distinguish from leukemia cutis [112]. (See 'Differential diagnosis' below.)

Serologic and other tests — Laboratory evaluation is useful for identifying findings consistent with Sweet syndrome (eg, leukocytosis) and signs of associated diseases or extracutaneous involvement. Our routine laboratory work-up for patients with suspected Sweet syndrome includes the following:

Complete blood count with platelets and differential

Complete metabolic panel

Erythrocyte sedimentation rate or C-reactive protein

Urinalysis

Pregnancy test in women of childbearing age

Additional laboratory studies are ordered based upon suspicion for specific sites of extracutaneous disease and associated underlying disorders. For example, patients with pulmonary symptoms, pleuritis, or hypoxia should have a chest radiograph to look for signs of pulmonary involvement. Examples of additional investigations for an underlying disorder include searches for evidence of recent streptococcal infection or an occult malignancy.

Evaluation for malignancy — Malignancy testing should only be considered in the setting of reasonable clinical suspicion for an underlying malignancy (eg, constitutional symptoms such as weight loss) and the absence of another explanation for a Sweet syndrome diagnosis (ie, pregnancy, drug exposure, recent infection, inflammatory bowel disease, rheumatoid arthritis, etc.). The screening for malignancy should begin with age-appropriate cancer screening guidelines. Some experts have proposed a work-up based upon the most common malignancies reported in association with Sweet syndrome [9]. This includes a physical examination that incorporates thyroid and lymph node examinations, as well as breast, cervical, uterine, and ovarian cancer screening in women and prostate and testicular examinations in men. Additional tests considered by these authors include a carcinoembryonic antigen level, colon cancer screening, and a chest radiograph. Other authors have suggested the use of chest, abdomen, and pelvis CT imaging or PET-CT imaging to evaluate for malignancy in patients with paraneoplastic conditions and reasonable suspicion for a malignancy of unknown source; this is similar to the literature for malignancy work-up of dermatomyositis, which is largely driven by expert opinion [113-115].

DIFFERENTIAL DIAGNOSIS

Lesion morphology — The clinical differential diagnosis of Sweet syndrome is dependent upon lesion morphology. Data obtained from the clinical history, physical examination, pathology findings, and microbial studies are useful for distinguishing between Sweet syndrome and other conditions:

Erythematous, edematous plaques:

Cutaneous infection (bacterial, fungal, and mycobacterial)

Urticaria and urticarial vasculitis

Other neutrophilic dermatoses (eg, pyoderma gangrenosum, neutrophilic eccrine hidradenitis, Behçet syndrome, cutaneous metastatic Crohn disease)

Drug eruptions

Halogenoderma (eg, bromoderma, iododerma)

Nodules (including subcutaneous Sweet syndrome):

Cutaneous infection (eg, deep fungal infection, Majocchi's granuloma, atypical mycobacterial infection)

Malignancy (eg, lymphoma cutis, leukemia cutis, metastatic carcinoma)

Subcutaneous sarcoidosis

Vasculitis (particularly medium-vessel vasculitis such as cutaneous polyarteritis nodosa)

Erythema nodosum

Bullous lesions:

Bullous pyoderma gangrenosum

Bullous leukocytoclastic vasculitis

Autoimmune bullous diseases (eg, bullous pemphigoid, bullous systemic lupus erythematosus, inflammatory epidermolysis bullosa acquisita, linear IgA bullous dermatosis)

Infection with bullous and hemorrhagic or necrotic changes (eg, bullous cellulitis, vessel invasive infections such as aspergillosis, ecthyma gangrenosum).

Infection — Infection is one of the most important disorders to consider in the patient with clinical and/or histologic findings suggestive of Sweet syndrome. As in Sweet syndrome, fever, leukocytosis, and cutaneous lesions characterized by neutrophil-dense infiltrates may occur in bacterial sepsis. In addition, the lesions of Sweet syndrome can resemble local bacterial, fungal, or atypical mycobacterial infections.

Leukemia cutis — The findings of a retrospective study in which fluorescence in situ hybridization (FISH) was performed on preserved cutaneous specimens from five of six patients given a diagnosis of hematologic malignancy-associated histiocytoid Sweet syndrome suggest that the clinicopathologic findings of histiocytoid Sweet syndrome may be particularly difficult to distinguish from leukemia cutis [112]. Cytogenic abnormalities in lesional skin were identical to those found in prior bone marrow biopsy specimens in four of the five patients, suggesting that these four patients may have actually had leukemia cutis. Additional studies are necessary to determine the role FISH analysis should play in differentiating histiocytoid Sweet syndrome and leukemia cutis.

SUMMARY AND RECOMMENDATIONS

Overview – Sweet syndrome (acute febrile neutrophilic dermatosis) is an inflammatory disorder characterized by the presence of inflammatory papules, plaques, or nodules on the skin, systemic symptoms, and neutrophilic infiltration of the skin. (See 'Introduction' above.)

Classification – Sweet syndrome is often divided into three categories based on etiology: classical Sweet syndrome, malignancy-associated Sweet syndrome, and drug-induced Sweet syndrome (table 3). (See 'Classification' above.)

Classical Sweet syndrome includes cases of Sweet syndrome that are not associated with malignancy or drug exposure. The most common causes of malignancy-associated Sweet syndrome and drug-induced Sweet syndrome are acute myelogenous leukemia and granulocyte-colony stimulating factor (G-CSF), respectively. (See 'Classification' above.)

Clinical manifestations – The cutaneous lesions of Sweet syndrome are typically painful, erythematous to violaceous papules and plaques (picture 1A-F). Pseudovesiculation and pustule formation are often present. Bullous Sweet syndrome and subcutaneous Sweet syndrome are less common manifestations. (See 'Cutaneous' above.)

Associated clinical and laboratory findings – Fever, malaise, joint pain, and muscle pain often accompany the cutaneous lesions. Involvement of internal organs may also occur. Leukocytosis and elevations in the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are common laboratory findings. (See 'Associated symptoms' above and 'Extracutaneous disease' above and 'Associated laboratory findings' above.)

Diagnosis – A diagnosis of Sweet syndrome is made based upon both clinical and laboratory findings (table 1). Biopsies characteristically demonstrate a dense neutrophilic infiltrate in the dermis without vasculitis. (See 'Diagnosis' above.)

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Topic 13784 Version 17.0

References

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