Acute febrile neutrophilic dermatosis was first described by Robert Douglas Sweet in 1964 (hence the eponym Sweet syndrome). This condition is a reactive process characterized by the abrupt onset of tender, red-to-purple papules and nodules that coalesce to form plaques. These plaques usually occur on the upper extremities, face, or neck and are typically accompanied by fever and peripheral neutrophilia.[1, 2] Sweet syndrome can be divided into three types on the basis of the underlying trigger.[3]
The first and most common type is classic or idiopathic Sweet syndrome, which occurs predominantly in young women after a mild respiratory illness and may be linked to pregnancy, inflammatory bowel disease (IBD),[3, 4] vaccinations, other inflammatory disorders, and infections.[5]
The second type can manifest aggressively in concert with an underlying malignancy. In some reports, the lesions of Sweet syndrome are the first clue to an underlying malignancy.[6] It is important to note that cutaneous lesions can also occur in the context of an established neoplastic process, as well as a paraneoplastic syndrome.[3] Acute myelogenous leukemia (AML) is the most common neoplasm with which malignancy-associated Sweet syndrome occurs,[7, 8, 9] along with myelodysplastic syndrome (MDS).[5]
The third type is an iatrogenic form that is recognized on the basis of reports of a variety of therapies bringing about lesions. The agents most commonly implicated are those that increase granulocyte colony-simulating factor (G-CSF).[10, 11, 12, 13] Other agents that have caused this variant of Sweet syndrome include trimethoprim-sulfamethoxazole,[14] minocycline, levonorgestrel/ethinyl estradiol, and all-trans retinoic acid (ATRA; or tretinoin). In addition, multiple antineoplastic agents, biologic agents,[5] and radiotherapy[15] have been implicated in the onset of these lesions.
In general, Sweet syndrome responds well to oral corticosteroids. If untreated, however, it may persist for weeks or months and usually improves without scarring.[3] Recurrence has been reported mainly in idiopathic and malignancy-related Sweet syndrome.[3] In rare cases, crops of lesions recur and can persist indefinitely.[2] Cases associated with malignancy can present with bullous or ulcerative lesions, which can resemble atypical pyoderma gangrenosum. These lesions are often recalcitrant to treatment.[2, 10, 16, 17]
The diagnosis of Sweet syndrome is based on fulfillment of both clinical and histopathologic criteria. Characteristics that distinguish the lesions of Sweet syndrome from other neutrophilic dermatoses are (1) healing of the lesions without scarring and (2) absence of vasculitis on histopathologic examination.
Acute febrile neutrophilic dermatosis is a hypersensitivity reaction that occurs in response to systemic factors, such as hematologic disease, infection, inflammation, vaccination, or drug exposure.[2] The condition is neutrophil-mediated, as evidenced by its histopathologic appearance, associated neutrophilia, and response to medications that affect neutrophil activity.[2]
The association of exogenous G-CSF with the development of Sweet syndrome also supports the impact of neutrophils and related endogenous cytokines in the underlying process.[10, 12] G-CSF suppresses apoptosis and prolongs neutrophil survival in vivo in a CD34+ cell population. G-CSF levels are increased in the peripheral blood of patients with active Sweet syndrome, suggesting that high levels of G-CSF may correlate with the activity of disease.[11]
The functional properties of neutrophils, rather than the absolute number, is thought to be significant, in that patients with Sweet syndrome due to G-CSF develop lesions as the neutrophil count rapidly increases, despite a decreased absolute neutrophil count.[17] (See the Absolute Neutrophil Count calculator.) In addition to G-CSF, the use of ATRA in the context of acute promyelocytic leukemia has shown the propagation of aberrant neutrophils as seen in drug-induced Sweet syndrome.[18]
Some studies have suggested a role for cytokines such as interleukin (IL)-1, IL-2, and interferon gamma (IFN-γ) in concert with type 1 helper T (Th1) cells, which may contribute to the pathogenesis of Sweet syndrome.[19] This is especially apparent with the malignancy-related form of the syndrome, in which patients who are given G-CSF, IFN-γ, and ATRA develop the characteristic lesions.[20] Studies have observed increased IL-6 with increasing disease activity and concomitant decrease in IL-6 after corticosteroids are used.[21, 22]
A possible genetic link with human leukocyte antigen (HLA)-B54 has been observed in the Japanese population.[23] A report of two brothers who developed Sweet syndrome in the neonatal period also supported a genetic predisposition.[24] Structural alterations in the long arm of chromosome 3 (3q) have been seen in association with Sweet syndrome; these changes involve genes that affect the regulation of granulopoiesis and neutrophil migration.[24]
Another genetic link is HLA-Cw1, which has been observed in neurologic Sweet syndrome.[23, 25] In addition, mutations in fms-like tyrosine kinase-3 have been associated with Sweet syndrome‒like skin disease, which has presented with mutated progenitors of neutrophils.[26, 27]
Potential causes of Sweet syndrome (acute febrile neutrophilic dermatosis) are numerous and depend on the type. In one case series of 176 patients, classic or idiopathic Sweet syndrome was the most common presentation and accounted for more than 71% of cases; Sweet syndrome associated with malignancy or an underlying condition (eg, infection or inflammatory disease) accounted for approximately 27% of the cases.[28]
Most of the underlying malignancies reported in the literature have been hematopoietic (most commonly AML),[7, 8, 28] but some have been due to solid tumors, mostly involving the genitourinary (GU) tract, breast, and gastrointestinal (GI) tract.[6] Finally, approximately 2% of cases overall have been associated with pregnancy.[29, 28, 30]
Hematologic malignancies
Several myeloid hematologic malignancies have been associated with Sweet syndrome, including myelodysplasia,[7] chronic myelogenous leukemia (CML),[31] and AML, including the promyelocytic (M3) variant of AML.[8]
Other nonmyeloid hematologic malignancies reported to occur in conjunction with Sweet syndrome include mycosis fungoides, Hodgkin disease, cutaneous T-cell lymphoma, non-Hodgkin lymphoma, hairy cell leukemia, and multiple myeloma; patients with immunoglobulin G (IgG) secretion may be at increased risk for Sweet syndrome.[32, 33, 34]
Nonhematologic malignancies
These rare associations include osteosarcoma, oral or tonsil cancer, ovarian cancer, thyroid cancer, lung cancer, pheochromocytoma, and cervical and rectal carcinoma.[17, 34, 35]
GU, breast, and GI cancers have also been reported in patients with Sweet syndrome.[7]
Infections
Multiple infections have been associated with Sweet syndrome, often involving the upper respiratory tract. Streptococcal pneumonia is the most commonly implicated infection.[36]
Other bacteria that can lead to Sweet syndrome include Salmonella species, Staphylococcus species, Francisella tularensis, Yersinia enterocolitica, Entamoeba coli, Helicobacter pylori, Borrelia burgdorferi, tuberculous mycobacteria, Mycobacterium chelonae, and Penicillium species.[36, 37, 38] Yersinia-associated Sweet syndrome has been noted to improve with antibiotics.[39]
Fungal infections have also been linked to the onset of Sweet syndrome; the syndrome may be a presenting feature of coccidiomycosis and has been associated with sporotrichosis.[40, 41] Viral agents such as HIV, cytomegalovirus (CMV), hepatitis A virus (HAV), hepatitis B virus (HBV), and parvovirus B19 have also been implicated.[42, 43]
Iatrogenic factors
Because the dominant cell in the dermal infiltrate of Sweet syndrome is the neutrophil, drug-induced Sweet syndrome is not considered to be a drug hypersensitivity. G-CSF is a well-established factor[2] ; other established factors include trimethoprim-sulfamethoxazole, ATRA, and minocycline, all of which have appeared in more than one case report.[14] It should be noted that multiple reports detailing drugs as causes of Sweet syndrome have involved patients with underlying malignancy; therefore, the specific causal link between drugs and Sweet syndrome is still unclear.[2] Anecdotal or limited reports of drug or device associations have included the following:
A more complete list of drugs reported to be associated with Sweet syndrome can be found in a review by Nelson et al, though not all of these agents were explicitly described as causing drug-induced Sweet syndrome.[5]
Systemic disorders
Associated inflammatory disease can be identified in about 16% of patients with Sweet syndrome.[28] The most common inflammatory conditions are Crohn disease and ulcerative colitis, which some authors consider part of a continuum of neutrophilic dermatosis.[67]
Sjögren syndrome, Behçet disease, lupus erythematosus, rheumatoid arthritis, familial Mediterranean fever, and undifferentiated connective-tissue disease have also been reported in association with Sweet syndrome.[2, 68]
Miscellaneous causes
Rare cases of Sweet syndrome have occurred with spinal surgery, sarcoidosis, erythema nodosum, relapsing polychondritis, thyroiditis, and systemic lupus erythematosus (SLE).[2, 69, 70, 71, 72]
About 2% of cases have been reported in the context of pregnancy.[2, 29, 30, 73]
Several cases of Sweet syndrome have occurred with polycythemia vera.[74]
One patient had a mutation in the prothrombin gene (G20210A), but no conclusive association has been established.[75]
A few cases of Sweet syndrome have been reported in transplant patients, including those undergoing bone marrow and kidney transplantation. Although these patients are taking immunomodulatory medications, an immune-mediated state has been described to explain the manifestation of Sweet syndrome in this patient population.[76]
Sweet syndrome as a manifestation of HIV-associated immune reconstitution inflammatory syndrome has been suggested.[77]
There have also been multiple reports of Sweet syndrome induced by radiotherapy.[15, 78, 79, 80]
Sweet syndrome (acute febrile neutrophilic dermatosis) has been listed as a rare disease by the National Organization for Rare Disorders (NORD),[81] with only a few hundred cases in the literature (~80 in children), but it is possible that it is underreported and thus may be better described as uncommon.[82] In several series, 10-20% of cases have occurred in a setting of malignancy, though most are idiopathic or associated with benign conditions.[14, 16]
Age-, sex-, and race-related demographics
Typically, women with Sweet syndrome are between the ages of 30 and 50 years.[2] However, cases in neonates as young as 5 days have been described.[83] In children, Sweet syndrome is extremely rare and is generally associated with infection.[84] Sweet syndrome occurring in children should prompt a workup for possible infection or immunodeficiency,[84] as well as a thorough workup to rule out malignancy.
The predilection for sex appears to depend on the type of Sweet syndrome. Classic or idiopathic Sweet syndrome has a female predominance, with a female-to-male ratio reported to be between 3:1 and 8:1.[5] Drug-induced Sweet syndrome appears also to have a female predilection.[3] However, malignancy-associated Sweet syndrome does not appear to share this predilection.[3, 7] No sex predilection has been observed in children.[84]
Sweet syndrome has no known racial predilection.[2]
Most cases of acute febrile neutrophilic dermatosis resolve, though some persist indefinitely and can be difficult to manage because of pain and skin breakdown. Because Sweet syndrome can be associated with many other diseases, including malignancy, the patient's overall prognosis depends on the underlying cause.[29] As many as 50% of patients may experience recurrence, most often in cases associated with hematologic malignancy or drug reactions.
Patient education should include information about the variable course of this condition, as well as advice on self-monitoring for signs and symptoms of other diseases.
In Sweet syndrome (acute febrile neutrophilic dermatosis), fever typically precedes the appearance of lesions by several days to weeks; however, fever and lesions may also occur simultaneously.[2] Many patients report an upper respiratory tract infection, tonsillitis, or flulike syndrome 1-3 weeks before the onset of skin lesions.[2, 85] Recent vaccination or a gastrointestinal (GI) tract infection may also precede the eruption.[54, 86]
The crop of plaques or nodules in the classic form often appears abruptly and may persist for days to several months if untreated.[2, 86]
Typical skin lesions are bright-red, reddish-blue, or violet papules, plaques, or nodules. (See the image below.) Massive subepidermal edema can produce a deceptively vesicular appearance, with pustules sometimes studding the lesions. Papules often coalesce into circinate or arcuate plaques.[2, 16, 85, 86] Plaques can cause pain and burning, but they are not pruritic. Lesions spontaneously resolve without scarring.[2]
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Red nodules and plaques on lateral aspect of hand.
The face, neck, and extremities are primarily affected in Sweet syndrome, characteristically in an asymmetric distribution.[2] However, several reports note atypical distribution of lesions. One report described lesions in the external auditory canal and tympanic membrane.[87] Facial or giant cellulitis–like,[88] necrotizing fasciitis type, subcutaneous types, and photodistributed violaceous plaques with heliotrope rash, malar erythema, scalp involvement (see the images below), and Gottron-like papules[89] are other clinical subtypes that have been reported.[90]
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Multiple lesions on scalp. Image from Alexa F Boer Kimball, MD, MPH.
View Image
Close-up of scalp lesion. Image from Alexa F Boer Kimball, MD, MPH.
Ulcers and bullae are more common in malignancy-associated disease than in other forms. These lesions may be extensive and generally are hard to treat.[86]
Sweet syndrome of the hands
Not uncommonly, Sweet syndrome may involve lesions on the dorsum of the hand. The lesions are predominantly distributed over the dorsal aspects of the fingers and hands in a roughly symmetrical pattern, with possible involvement of other extensor surfaces.[85]
Oral and ocular mucosal manifestations
Sweet syndrome can also manifest in the oral cavity or eyes. It is known to give rise to oral lesions on the lips, buccal mucosa, or tongue; these lesions most commonly appear in context of a hematologic disorder.[10] Conjunctivitis and episcleritis are the most common ocular manifestations; others that have been reported include uveitis, limbal nodules, glaucoma, subconjunctival hemorrhage, scleritis, iritis, and sudden visual loss.[91, 92, 93]
Extracutaneous manifestations
Sweet syndrome can involve extracutaneous organ systems as well.[2] Pulmonary involvement may manifest as dyspnea, chronic cough, or pulmonary infiltrates or effusions on chest radiographs. In rare cases, symptoms may become severe enough to cause respiratory failure or bronchiolitis obliterans organizing pneumonia. Fortunately, most of these cases are highly responsive to corticosteroid therapy.[40, 94, 95, 96]
Renal involvement can be demonstrated by the presence of proteinuria, hematuria, and decreased creatinine clearance.[2] (See the Creatinine Clearance [measured] calculator.)
Other sites that have been reported include the bones, intestines, joints, bone marrow, liver, heart, muscles, and spleen.[2, 13, 33, 9, 97, 98, 99, 100, 101, 102]
A few cases of systemic inflammatory response syndrome (SIRS) progressing to shock and organ dysfunction have been reported, with rapid improvement achieved through administration of high-dose intravenous (IV) methylprednisolone. The efficacy of treatment highlights the association of SIRS with Sweet syndrome, which can be hard to distinguish from infection.[103, 104, 105]
Among children, cases of acquired cutis laxa have been reported in lesions consistent with Sweet syndrome.[106] A 2-year-old girl diagnosed with both Sweet syndrome and cutis laxa was found to have acute necrosis in the cardiac apex and interventricular septum and focal chronic inflammatory and granulation tissue in the aortic wall.[107] The authors suggested that children with both Sweet syndrome and cutis laxa should undergo complete cardiac evaluation by a pediatric cardiologist because these findings could indicate a potentially fatal condition.
A 2017 study found that central nervous system (CNS) involvement had been reported in only 69 cases in the literature since 1986.[108] Encephalitis and meningitis are common neurologic manifestations in these cases.[23] The most common symptoms reported are headaches, altered consciousness, and seizures.[23] There may be a genetic link; an association between human leukocyte antigen (HLA)-B54 and HLA-Cw1 and CNS-related Sweet syndrome was reported in a population of Japanese patients.[23]
CNS-related Sweet syndrome can be differentiated from Behçet syndrome, in that the latter features more progressive and severe CNS involvement, whereas Sweet syndrome involves the CNS transiently, though recurrences may develop.[23] It should be noted that there can be a delay of up to 10 years from the onset of neurologic symptoms to the onset of the characteristic skin lesions.[25]
In addition to CNS involvement, peripheral neuropathy has been reported.[23] Cerebrospinal fluid (CSF) pleocytosis has also been described, as has sterile chronic recurrent multifocal osteomyelitis in children.[109]
Ocular involvement has been reported as well, characterized by conjunctivitis, scleritis, iritis, choroiditis, and retinal vasculitis. Such involvement can be sight-threatening.[110]
Pathergy
Like pyoderma gangrenosum, Sweet syndrome is known to cause pathergy in which lesions occur in areas of minor trauma, such as sites of scratches, bites, and venipuncture.[36] The lesions may also be photodistributed or localized to the site of a previous phototoxic reaction (eg, sunburn).[2, 36]
Underlying disease
It is important to recognize and treat any associated or underlying systemic diseases or malignancies. Sweet syndrome may be a clue to the diagnosis of a systemic disorder or malignancy.[111] Imaging studies, such as ultrasonography (US), computed tomography (CT), positron-emission tomography (PET), or magnetic resonance imaging (MRI), may be helpful in identifying such underlying malignancies.
Pregnancy
Sweet syndrome can occur during pregnancy and may recur in subsequent pregnancies. At present, it is not believed to be associated with fetal harm.[29]
Diagnostic criteria
Classic or idiopathic Sweet syndrome
The diagnosis of classic or idiopathic Sweet syndrome, as first proposed by Su and Liu[112] and subsequently revised by von den Driesch,[28] depends on the presence of both major criteria and at least two of four minor criteria.
Major criteria are as follows:
Abrupt onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules, or bullae
Predominantly neutrophilic infiltration in the dermis without leukocytoclastic vasculitis per microscopic examination of a biopsy sample
Minor criteria are as follows:
Association with an underlying disorder or condition, such as (1) respiratory tract infection, (2) GI tract infection, (3) vaccination, (4) inflammatory disease, (5) hematoproliferative disorder, (6) solid malignant tumor, or (7) pregnancy
Pyrexia (temperature >38°C [100.4°F])
Abnormalities in at least three of the following four laboratory tests during onset: (1) elevated erythrocyte sedimentation rate (ESR) (>20 mm), (2) positive C-reactive protein (CRP) result, (3) peripheral blood smear showing segmented nuclear neutrophils, bands >70%, (4) leukocytosis (>8000/µL)
Excellent response to treatment with systemic corticosteroids or potassium iodide
Drug-induced Sweet syndrome
The diagnosis of drug-induced Sweet syndrome (as proposed by Walker and Cohen[14] ) is made if all five of the following criteria are met:
Abrupt onset of painful erythematous plaques or nodules
Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
Pyrexia (temperature >38°C [100.4°F])
Temporal relation between drug ingestion and clinical presentation, or temporally related recurrence after oral challenge
Temporally related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids
The diagnosis of Sweet syndrome (acute febrile neutrophilic dermatosis) includes histopathologic evidence per the criteria mentioned in Physical Examination. Clinicopathologic correlation is important because bowel bypass syndrome may present with skin lesions with an identical histologic picture.[2, 29, 86]
Although laboratory tests can be nonspecific, the tests described below can be helpful in the diagnosis and further workup for Sweet syndrome, especially in the course of investigating for an underlying cause.
A complete blood count (CBC) with differential must be ordered to detect for minor criteria and to screen for hematologic disorder or malignancy. Neutrophilia is typically present, but the absence of neutrophilia in a patient who is neutropenic does not rule out Sweet syndrome. Anemia and thrombocytopenia are common in patients with underlying malignancy. Abnormalities in the CBC should prompt consideration of bone marrow biopsy.[2, 85, 86]
The erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP) level, or both may be elevated. One report noted that ESR is elevated in more than 90% of cases.[86] However, both of these findings are nonspecific manifestations of inflammation.[2, 86]
Urinalysis may show proteinuria and/or hematuria.[7]
Hepatic panel may show nonspecific elevation of hepatic enzymes.[36]
Antineutrophilic cytoplasmic antibodies (ANCAs) have been described but have not been consistently found in all patients with Sweet syndrome.[113]
Lesions should be cultured for bacteria, fungi, and mycobacteria to rule out infection.[2]
A chest radiograph should be obtained if pulmonary symptoms of Sweet syndrome are present because this form is responsive to systemic corticosteroids.[29]
Sweet syndrome is the presenting sign of malignancy in approximately two thirds of the cases of malignancy-associated Sweet syndrome.[29] For this reason, the presence of ulcerative lesions, oral lesions, abnormal platelet counts, or anemia should prompt investigation for an underlying malignancy.[7] Some authors have recommended a complete systemic evaluation in all patients with Sweet syndrome.[28] If an underlying malignancy is suspected, the appropriate imaging modality should be used for early detection and treatment.[2]
2-[Fluorine 18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) is especially useful in evaluating myeloproliferative disorders, but it can also be helpful in assessing some solid tumors and has successfully depicted early malignancies.[114]
Skin biopsy should be performed to confirm the diagnosis of Sweet syndrome (acute febrile neutrophilic dermatosis) per the major diagnostic criteria previously described (see Physical Examination).[2]
Bone marrow aspiration is indicated if the CBC is abnormal, and it should be considered in all cases of atypical bullous or ulcerative Sweet syndrome to assess for myelodysplastic disease.[92]
Age-appropriate cancer screening and evaluation for inflammatory bowel disease (IBD) are indicated if no other underlying cause is found, especially in patients with bullous or ulcerative lesions.[2]
The classic histopathologic pattern of Sweet syndrome consists of a dense, diffuse neutrophilic infiltrate in the reticular dermis. Leukocytoclastic nuclear debris is typically present interstitially, and massive papillary dermal edema is common. True vasculitic changes (expansion of postcapillary venule wall with fibrin deposition) are absent. Eosinophils and lymphocytes are present in some instances, but neutrophils usually predominate.[2]
The epidermis usually is spared, though nonspecific findings such as spongiosis and subcorneal pustule formation can be seen.[86]
Results of direct immunofluorescence testing are noncontributory. In rare cases, the inflammation extends to involve the subcutis. In essentially all instances, cases with subcutaneous involvement also show extensive involvement of the reticular dermis.[86]
Histiocytoid Sweet syndrome is a variant that has been described and includes histiocytoid cells, which are immature myeloid cells commonly mistaken for histiocytes. The most important differential diagnosis for this variant is leukemia cutis.[115] Other histologic variants include lymphocytic, subcutaneous, and crytococcoid types.[90]
The best-documented first-line options for treatment of acute febrile neutrophilic dermatosis (Sweet syndrome) are systemic corticosteroids or topical steroids if the lesions are limited. If the use of corticosteroids is contraindicated, anti-inflammatory agents such as dapsone or colchicine can be used as alternative first-line therapies.
If an underlying disorder is identified, successful treatment of that disorder may promote resolution of Sweet syndrome and prevent recurrences.[29, 86] Otherwise, in most cases of Sweet syndrome, prednisone 0.5-1 mg/kg/day is extremely and rapidly effective.[2, 5, 28] In more severe presentations, prednisone 2 mg/kg/day in two divided doses is warranted.[5] Pulmonary infiltrates also tend to respond promptly to prednisone.[94]
Despite the excellent response, recurrences of neutrophilic dermatitis are common and generally develop as steroid use is being tapered; therefore, a slow taper is recommended.[5] If the underlying disease flares, more time may be needed for effective tapering of therapy.[2] High-potency topical steroids (eg, clobetasol propionate 0.05%) or intralesional glucocorticoids (eg, triamcinolone acetonide 3-10 mg/mL) may also be useful in localized lesions.[29]
In the pediatric population, long-term use of corticosteroids can cause problems with linear growth, blood pressure, and blood glucose levels. Children may also have social sequelae associated with their use. Therefore, attempts are usually made to treat children with steroid-sparing drugs.[24] A case of cutis laxa–like lesions in skin previously affected by Sweet syndrome 9 months after presentation and treatment with corticosteroids has been described in an 8-month-old child.[106]
For long-term management, numerous drugs may be helpful. Although the mechanism of many of these medications is inhibition of neutrophil chemotaxis, none have been shown to be more efficacious than corticosteroids.[2, 29]
Indomethacin, colchicine, and potassium iodide were found to be helpful in small series of patients.[1, 2, 116, 117] One retrospective study evaluating 90 patients with acute febrile neutrophilic dermatosis demonstrated effective use of colchicine as first-line therapy.[118]
Dapsone, cyclosporine, etretinate, pentoxifylline, and clofazimine have been used, with anecdotal success.[2, 23, 28, 119]
Doxycycline, metronidazole, isotretinoin, methotrexate, cyclophosphamide, chlorambucil, adalimumab, infliximab, intravenous immunoglobulin (IVIG), pulse doses of methylprednisolone, and interferon alfa have also reported to yield some success.[2, 23, 28, 119, 120, 121, 122, 123]
In the treatment of recalcitrant Sweet syndrome, thalidomide has been used to clear lesions within 1 month after therapy with corticosteroids, metronidazole, dapsone, and methotrexate failed.[124]
Several reports have described successful treatment of Sweet syndrome with biologic agents. In a small case series of rheumatoid arthritis patients, etanercept was reported to control the skin manifestations of acute febrile neutrophilic dermatosis.[125] However, care must be taken when this treatment is used in a group with concomitant or a high likelihood of cancer.[126] Anakinra and rituximab have also been reported to be effective in refractory cases.[127, 128] In addition, successful use of adalimumab to treat a recalcitrant case of Sweet syndrome has been reported.[129] A more complete list of therapies can be found in a review by Nelson et al.[5]
Consultation with a dermatologist is indicated for the diagnosis and evaluation of underlying causes of Sweet syndrome. An internal medicine specialist may be consulted to evaluate any underlying or triggering conditions.
Outpatient care for the skin lesions of Sweet syndrome is usually coordinated by a dermatologist in conjunction with other physicians who may be involved if other underlying diseases are present.
What is acute febrile neutrophilic dermatosis (Sweet syndrome)?What is the pathophysiology of acute febrile neutrophilic dermatosis (Sweet syndrome)?What causes acute febrile neutrophilic dermatosis (Sweet syndrome)?Which malignancies are associated with acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the infectious causes of acute febrile neutrophilic dermatosis (Sweet syndrome)?Which medications cause acute febrile neutrophilic dermatosis (Sweet syndrome)?Which systemic disorders are associated with acute febrile neutrophilic dermatosis (Sweet syndrome)?What are rare causes of acute febrile neutrophilic dermatosis (Sweet syndrome)?What is the prevalence of acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the racial predilections of acute febrile neutrophilic dermatosis (Sweet syndrome)?What is the sex predilection of acute febrile neutrophilic dermatosis (Sweet syndrome) by gender?How does the incidence of acute febrile neutrophilic dermatosis (Sweet syndrome) vary by age?What is the prognosis of acute febrile neutrophilic dermatosis (Sweet syndrome)?What is included in patient education about acute febrile neutrophilic dermatosis (Sweet syndrome)?Are the signs and symptoms of acute febrile neutrophilic dermatosis (Sweet syndrome)?How are the cutaneous lesions of acute febrile neutrophilic dermatosis (Sweet syndrome) characterized?Which physical findings suggest acute febrile neutrophilic dermatosis (Sweet syndrome) of the hands?Which oral and mucosal findings suggest acute febrile neutrophilic dermatosis (Sweet syndrome) of the hand?Which extracutaneous findings suggest acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the signs of pathergy in patients with acute febrile neutrophilic dermatosis (Sweet syndrome)?How are systemic disease or malignant causes of acute febrile neutrophilic dermatosis (Sweet syndrome) identified?How does acute febrile neutrophilic dermatosis (Sweet syndrome) affect pregnancy outcomes?What are the diagnostic criteria for classic or idiopathic acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the diagnostic criteria for drug-induced acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the possible complications of acute febrile neutrophilic dermatosis (Sweet syndrome)?Which conditions should be included in the differential diagnoses of acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the differential diagnoses for Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome)?What is the role of lab testing in the workup of acute febrile neutrophilic dermatosis (Sweet syndrome)?What is the role of imaging studies in the workup of acute febrile neutrophilic dermatosis (Sweet syndrome)?What procedures are used for the workup of acute febrile neutrophilic dermatosis (Sweet syndrome)?When is bone marrow aspiration performed in the workup of acute febrile neutrophilic dermatosis (Sweet syndrome)?Which tests should be considered if no underlying cause of acute febrile neutrophilic dermatosis (Sweet syndrome) is found?Which histologic findings are characteristic of acute febrile neutrophilic dermatosis (Sweet syndrome)?How is acute febrile neutrophilic dermatosis (Sweet syndrome) treated?Which medications are used for long-term management of acute febrile neutrophilic dermatosis (Sweet syndrome)?How is acute febrile neutrophilic dermatosis (Sweet syndrome) prevented?Which specialist consultations are beneficial to patients with acute febrile neutrophilic dermatosis (Sweet syndrome)?Who provides long-term monitoring of patients with acute febrile neutrophilic dermatosis (Sweet syndrome)?What are the goals of drug treatment for acute febrile neutrophilic dermatosis (Sweet syndrome)?Which medications in the drug class Corticosteroids, Topical are used in the treatment of Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome)?Which medications in the drug class Corticosteroids are used in the treatment of Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome)?
Yoon-Soo (Cindy) Bae, MD, Clinical Assistant Professor, Ronald O Perelman Department of Dermatology, New York University School of Medicine; Procedural Dermatologist, Laser and Skin Surgery Center of New York
Disclosure: Nothing to disclose.
Coauthor(s)
Edward Bae, MD, Resident Physician, Department of Dermatology, Roger Williams Medical Center
Disclosure: Nothing to disclose.
Sharon A Salter, MD, Staff Physician, Department of Psychiatry, Tufts-New England Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology
Disclosure: Nothing to disclose.
Rosalie Elenitsas, MD, Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.
Chief Editor
William D James, MD, Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.
Additional Contributors
Timothy McCalmont, MD, Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology
Disclosure: Received consulting fee from Apsara for independent contractor.
Acknowledgements
Christina N Alavian, MD, Resident Physician, Division of Dermatology, University of Massachusetts Medical School
Disclosure: Nothing to disclose.
Alexa F Boer Kimball, MD, MPH Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Sweet syndrome. National Organization for Rare Disorders. Available at https://rarediseases.org/rare-diseases/sweet-syndrome/. October 15, 2015; Accessed: February 12, 2025.