Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome) 

Updated: Jun 02, 2020
Author: Yoon-Soo (Cindy) Bae, MD; Chief Editor: William D James, MD 

Overview

Background

Robert Douglas Sweet first described acute febrile neutrophilic dermatosis in 1964, leading to the eponym Sweet syndrome (SS).[1] 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.[2] Sweet syndrome can be divided into three categories based on the underlying trigger.[3]

First, the 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,[4] inflammatory bowel disease,[3, 5] vaccinations, other inflammatory disorders, and infections.[6]

Second, Sweet syndrome can manifest aggressively in concert with an underlying malignancy. In some reports, the lesions of Sweet syndrome are the first clue of underlying malignancy.[7] 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 is the most common neoplasm with which malignancy-associated Sweet syndrome occurs,[8, 9] as well as myelodysplastic syndrome.[6]

Finally, an iatrogenic form of Sweet syndrome is recognized based on reports of a variety of therapies bringing about lesions. The most commonly implicated agents 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 (Bactrim), minocycline, levonorgestrel/ethinyl estradiol, and all-trans retinoic acid (ATRA).[14] In addition, multiple antineoplastic agents, biologic agents,[6] and radiotherapy[15] have also been implicated in the onset of these lesions.

In general, Sweet syndrome responds well to oral corticosteroids; however, without treatment, the syndrome 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 healing of the lesions without scarring and an absence of vasculitis on histopathological examination.

Pathophysiology

Sweet syndrome (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 the survival of neutrophils in vivo in a CD34+ cell population. G-CSF levels are increased in 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 because 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-γ (IFN-γ) in concert with type 1 helper T cells, which may contribute to the pathogenesis of Sweet syndrome.[19] This is especially apparent in the malignancy-related form of Sweet syndrome, in which patients who are given G-CSF, IFN-γ, and ATRA develop the characteristic lesions.[20] More recent 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 HLA-B54 has been observed in the Japanese population.[23] A report of two brothers who developed Sweet syndrome in the neonatal period also supports 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]

Etiology

Potential causes Sweet syndrome (acute febrile neutrophilic dermatosis) are numerous and depend on the subtype. 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.[28] 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 are hematopoietic (most commonly acute myeloid leukemia),[8, 9, 28] but some are due to solid tumors, mostly involving the genitourinary tract, breast, and gastrointestinal tract.[7] Finally, approximately 2% of cases overall were associated with pregnancy.[4, 28, 29]

Hematologic malignancy–related Sweet syndrome

Several myeloid hematologic malignancies have been associated with Sweet syndrome, including myelodysplasia,[8] chronic myelogenous leukemia,[30] and acute myeloid leukemia, including the promyelocytic (M3) variant of acute myeloid leukemia.[9]

Other nonmyeloid hematologic malignancies reported to co-occur with Sweet syndrome include mycosis fungoides, Hodgkin disease, cutaneous T-cell lymphoma, non-Hodgkin lymphoma, hairy cell leukemia, and multiple myeloma, as patients with immunoglobulin G secretion may be at increased risk for Sweet syndrome.[31, 32, 33]

Nonhematologic malignancy–related causes of Sweet syndrome

These rare associations include osteosarcoma, oral cancer/tonsil cancer, ovarian cancer, thyroid cancer, lung cancer, pheochromocytoma, and cervical and rectal carcinoma.[17, 33, 34]

Genitourinary, breast, and gastrointestinal cancers have also been reported in patients with Sweet syndrome.[8]

Infection-related causes of Sweet syndrome

Multiple infections have been associated with Sweet syndrome, often involving the upper respiratory tract. Streptococcal pneumonia is the most commonly implicated infection.[35]

Other bacterial culprits 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.[35, 36, 37]

Notably, Yersinia-associated Sweet syndrome has been noted to improve with antibiotics.[38]

Fungal infections have also been linked in the onset of Sweet syndrome, as it may be a presenting feature of coccidiomycosis and has been associated with sporotrichosis.[39, 40] Viral agents such as HIV, cytomegalovirus (CMV), hepatitis A, hepatitis B, and parvovirus B19 have also been implicated.[41, 42]

Iatrogenic causes of Sweet syndrome

Because the dominant cell in the dermal infiltrate of Sweet syndrome is the neutrophil, drug-induced Sweet syndrome is not considered to a drug hypersensitivity. Granulocyte colony-stimulating factor (G-CSF) is a well-established factor.[2, 43] Established factors include trimethoprim-sulfamethoxazole (Bactrim), all-trans retinoic acid (ATRA), and minocycline, which have all appeared in more than one case report.[14] It is important to note that multiple reports detail drugs to cause Sweet syndrome in patients with underlying malignancy; therefore, the causal link between drugs and Sweet syndrome is still unclear.[2] Anecdotal or limited reports of drug or device associations include the following[44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65] :

  • Lithium
  • Furosemide
  • Hydralazine
  • Carbamazepine
  • Oral contraceptives
  • Mirena intrauterine device
  • COX-2 inhibitors
  • Azathioprine
  • Doxycycline
  • Diazepam
  • Diclofenac
  • Nitrofurantoin
  • Propylthiouracil
  • Lenalidomide
  • Bortezomib
  • Abacavir
  • imatinib
  • 5-Azacytidine
  • Decitabine
  • Interleukin (IL)–2
  • Clindamycin
  • Mitoxantrone
  • Vaccinations (eg, for BCG, smallpox, pneumococcal organisms, influenza)
  • Ticagrelor
  • Dapagliflozin
  • Erlotinib
  • Tocilizumab
  • Hydroxychloroquine
  • Dabrafenib and trametinib
  • Mesalamine
  • Ibrutinib
  • Ipilimumab
  • Fluconazole

A more complete list of drugs reported to be associated with drug-induced Sweet syndrome can be found in a review by Nelson et al, although not all of these agents were reported to explicitly cause drug-induced Sweet syndrome.[6]

Systemic disorder–related causes of Sweet syndrome

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.[66]

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, 67]

Miscellaneous causes of Sweet syndrome

Rare cases of Sweet syndrome have occurred with spinal surgery, sarcoidosis, erythema nodosum, relapsing polychondritis, thyroiditis, and systemic lupus erythematosus.[2, 68, 69, 70, 71]

Two percent of cases have been reported in the context of pregnancy.[2, 4, 29]

Several cases of Sweet syndrome have occurred with polycythemia vera.[72]

One patient had a mutation in the prothrombin gene (G20210A), but no conclusive association can be made at this time.[73]

A few cases of Sweet syndrome have been reported in the literature in transplantation 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.[74]

Sweet syndrome as a manifestation of HIV-associated immune reconstitution inflammatory syndrome has been suggested.[75]

There are also multiple reports of Sweet syndrome induced by radiotherapy.[15, 76, 77, 78]

Epidemiology

Frequency

Sweet syndrome (acute febrile neutrophilic dermatosis) is uncommon but not rare. In several series, 10-20% of cases have occurred in a setting of malignancy, although most are idiopathic or associated with benign conditions.[14, 16]

Race

Sweet syndrome has no known racial predilection.[2]

Sex

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.[6]

Drug-induced Sweet syndrome appears also to have a female predilection.[3]

However, this predilection is not apparent in cases associated with malignancy.[3, 8]

No sex predilection has been observed in children.[79]

Age

Typically, women with Sweet syndrome are aged 30-50 years.[2] However, cases in neonates as young as 5 days have been described.[80] In children, Sweet syndrome is extremely rare and generally associated with infection.[79]

Sweet syndrome occurring in children should prompt a workup for possible infection or immunodeficiency,[79] as well as a thorough workup to rule out malignancy.

Prognosis

Most cases of Sweet syndrome (acute febrile neutrophilic dermatosis) resolve, although some persist indefinitely and can be difficult to manage because of pain and skin breakdown. Because this condition can be associated with many other diseases, including malignancy, the patient's overall prognosis depends on the underlying cause.[4] The outcome depends on the underlying condition, but recurrence may occur in up to 50% of patients and is most likely in cases associated with hematologic malignancy or drug reactions.

Patient Education

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.

 

Presentation

History

Typically, fever precedes the appearance of lesions in Sweet syndrome (acute febrile neutrophilic dermatosis) by several days to weeks; however, fever and lesions of may also occur simultaneously.[2] Many patients report an upper respiratory tract infection, tonsillitis, or flulike syndrome 1-3 weeks prior to onset of skin lesions.[2, 81] Recent vaccination or a gastrointestinal tract infection may also precede the eruption.[44, 82]

The crop of plaques or nodules in the classic form often appears abruptly and may persist for days to several months if untreated.[2, 82]

Physical Examination

Cutaneous manifestations of Sweet syndrome

Typical skin lesions are bright-red, reddish-blue, or violet papules, plaques, or nodules. Massive subepidermal edema can produce a deceptively vesicular appearance, with pustules sometimes studding these lesions. Papules often coalesce into circinate or arcuate plaques.[2, 16, 81, 82] Plaques can cause pain and burning, but they are not pruritic. Lesions spontaneously resolve without scarring.[2]

The face, neck, and extremities primarily are affected, characteristically in an asymmetric distribution.[2] However, several reports note atypical distribution of Sweet syndrome (acute febrile neutrophilic dermatosis) lesions. One report describes lesions in the external auditory canal and tympanic membrane.[83] Facial or giant cellulitis–like,[84] necrotizing fasciitis type, subcutaneous types, and photo-distributed violaceous plaques with heliotrope rash, malar erythema, scalp involvement, and Gottron-like papules[85] are other clinical subtypes reported.[86]

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.[82]

See the images below.

Multiple lesions on the scalp. Courtesy of Alexa F Multiple lesions on the scalp. Courtesy of Alexa F Boer Kimball, MD, MPH.
Close-up of a scalp lesion. Courtesy of Alexa F Bo Close-up of a scalp lesion. Courtesy of Alexa F Boer Kimball, MD, MPH.

Sweet syndrome of the hands

Sweet syndrome on the dorsum of the hand is not uncommon. 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.[81]

Sweet syndrome of the oral and ocular mucosae

Sweet syndrome can also manifest in the oral cavity or eyes. The condition is known to manifest as oral lesions on the lips, buccal mucosa, and/or tongue; these lesions most commonly appear in context of a hematologic disorder.[10] Conjunctivitis and episcleritis are the most common ocular forms. Other reported ocular manifestations include uveitis, limbal nodules, glaucoma, subconjunctival hemorrhage, scleritis, iritis, and sudden visual loss.[87, 88, 89]

Extracutaneous manifestations of Sweet syndrome

Sweet syndrome can involve extracutaneous organ systems.[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 glucocorticoid therapy.[39, 90, 91, 92]

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, 32, 45, 93, 94, 95, 96, 97, 98]

A few cases of systemic inflammatory response syndrome (SIRS) progressing to shock and organ dysfunction have been reported, with rapid improvement using high-dose intravenous methylprednisolone. The treatment efficacy highlights the association of SIRS with Sweet syndrome, which can be hard to distinguish from infection.[99, 100, 101]

Among children, cases of acquired cutis laxa have been reported in lesions consistent with Sweet syndrome.[102] 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. The authors suggest that children with both Sweet syndrome and cutis laxa undergo complete cardiac evaluation by a pediatric cardiologist, as these findings can indicate a potentially fatal condition.[103]

CNS involvement has been reported in 69 cases in the literature since 1986.[104] 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, as reports have shown an association between HLA-B54 and HLA-CW1 and CNS-related Sweet syndrome in a population of Japanese patients.[23] CNS Sweet syndrome can be differentiated from Behçet syndrome, as the latter features more progressive and severe CNS involvement, whereas Sweet syndrome transiently involves the CNS, although recurrences may occur.[23] Of note, there can be a delay of up to 10 years from the onset of neurological symptoms to the onset of the characteristic skin lesions.[25]

In addition to CNS involvement, peripheral neuropathy has also been reported.[23] Cerebrospinal fluid pleocytosis also has been described, as has sterile chronic recurrent multifocal osteomyelitis in children.[105]

Ocular involvement has also been reported, characterized by conjunctivitis, scleritis, iritis, choroiditis, and retinal vasculitis; ocular involvement can be sight-threatening.[106]

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.[35] The lesions may also be photodistributed or localized to the site of a previous phototoxic reaction (eg, sunburn).[2, 35]

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.[107] Imaging studies, such as ultrasonography, CT scanning, positron-emission tomography (PET) scanning, or MRI, may be helpful in identifying such underlying malignancies.

Pregnancy

Sweet syndrome can occur during pregnancy and may recur in subsequent pregnancies. Presently, it is believed that the disease is not associated with fetal harm.[4]

Diagnostic criteria

Classic or idiopathic Sweet syndrome

Classic or idiopathic Sweet syndrome, as proposed by Su and Liu[108] and revised by von den Driesch,[28] depends on the presence of both major criteria and at least two 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, including the following: (1) respiratory tract infection, (2) gastrointestinal tract infection, (3) vaccination, (4) inflammatory disease, (5) hematoproliferative disorders, (6) solid malignant tumors, (7) pregnancy
  • Pyrexia (temperature >38°C)
  • 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 (count >8000/µL)
  • Excellent response to treatment with systemic corticosteroids or potassium iodide

Drug-induced Sweet syndrome

Drug-induced Sweet syndrome (proposed by Walker and Cohen[14] ) is diagnosed 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 relationship 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

Complications

Generally, lesions resolve without scarring, although pigmentary changes may take months to fade.

 

DDx

Diagnostic Considerations

Also consider the following:

Differential Diagnoses

 

Workup

Laboratory Studies

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, 4, 82]

Although laboratory tests can be nonspecific, the tests described below can be helpful in the diagnosis and further workup for Sweet syndrome, especially when investigating for an underlying cause.

A complete blood cell (CBC) count 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 count should prompt consideration of bone marrow biopsy.[2, 81, 82]

Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) levels may be elevated. One report notes that ESR is elevated in more than 90% of cases.[82] However, both of these findings are nonspecific manifestations of inflammation.[2, 82]

Urinalysis may show proteinuria and/or hematuria.[8]

Hepatic panel may show nonspecific elevation of hepatic enzymes.[35]

Antineutrophilic cytoplasmic antibodies (ANCAs) have been described but not consistently found in all patients with Sweet syndrome.[109]

Lesions should be cultured for bacteria, fungi, and mycobacteria to rule out infection.[2]

Imaging Studies

A chest radiograph should be obtained if pulmonary symptoms of Sweet syndrome (acute febrile neutrophilic dermatosis) are present because this form is responsive to systemic corticosteroids.[4]

Sweet syndrome is the presenting sign of malignancy in approximately two thirds of the cases of malignancy-associated Sweet syndrome.[4] For this reason, the presence of ulcerative lesions, oral lesions, abnormal platelet counts, or anemia should prompt investigation for an underlying malignancy.[8] Some authors recommend 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.[110]

Procedures

Skin biopsy should be performed to confirm the diagnosis of Sweet syndrome (acute febrile neutrophilic dermatosis) per the major criteria listed in Physical Examination.[2]

Bone marrow aspiration is indicated if the CBC count is abnormal, and it should be considered in all cases of atypical bullous or ulcerative Sweet syndrome to detect for myelodysplastic disease.[88]

Age-appropriate cancer screening and evaluation for inflammatory bowel disease are indicated if no other underlying cause is found, especially in patients with bullous or ulcerative lesions.[2]

Histologic Findings

The classic histopathologic pattern of Sweet syndrome (acute febrile neutrophilic dermatosis) 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, although nonspecific findings such as spongiosis and subcorneal pustule formation can be seen.[82]

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.[82]

Histiocytoid Sweet syndrome is a variant that has been described and includes histiocytoid cells, which are immature myeloid cells commonly mistaken as histiocytes. The most important differential diagnosis for this variant is leukemia cutis.[111] Other histologic variants include lymphocytic, subcutaneous, and crytococcoid types.[86]

 

Treatment

Medical Care

If identified, successful therapy of the underlying disorder may promote resolution of Sweet syndrome (acute febrile neutrophilic dermatosis) and prevent recurrences.[4, 82] Otherwise, in most cases of Sweet syndrome, prednisone is extremely and rapidly effective, in doses of 0.5-1 mg/kg/day.[2, 6, 28] In more severe presentations, 2 mg/kg/day divided into two doses per day is warranted.[6] Pulmonary infiltrates also tend to respond promptly to prednisone.[90] 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.[6] If the underlying disease flares, it may take longer to effectively taper 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.[4]

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.[102]

For long-term management, numerous drugs may be helpful. Although the mechanism of many of these medications is inhibition of neutrophil chemotaxis, none has been shown to be more efficacious than corticosteroids.[2, 4]

Indomethacin, colchicine, and potassium iodide were helpful in small series of patients.[2, 112, 113] One retrospective study evaluating 90 patients with acute febrile neutrophilic dermatosis demonstrated the effective use of colchicine as first-line therapy.[114]

Dapsone, cyclosporine, etretinate, pentoxifylline, and clofazimine also have been used, with anecdotal success.[2, 23, 28, 115]

Doxycycline, metronidazole, isotretinoin, methotrexate, cyclophosphamide, chlorambucil, adalimumab, infliximab, intravenous immunoglobulin (IVIG), pulse doses of methylprednisolone, and interferon-alfa are also reportedly successful.[2, 23, 28, 115, 116, 117, 118, 119]

In the treatment of recalcitrant acute febrile neutrophilic dermatosis, thalidomide has been used to clear lesions within 1 month after therapy with corticosteroids, metronidazole, dapsone, and methotrexate failed.[120]

Several reports describe biologic agents successfully treating Sweet syndrome. Etanercept has been reported to control the skin manifestations of acute febrile neutrophilic dermatosis in a small case series of rheumatoid arthritis patients.[121] However, care must be taken when using this treatment in a group with concomitant or a high likelihood of cancer.[122] Anakinra and rituximab have also been reported to be effective in refractory cases.[123, 124] In addition, adalimumab has been reported to successfully treat a recalcitrant case of Sweet syndrome.[125] A more complete list of therapies can be found in a review by Nelson et al.[6]

Consultations

Consultation with a dermatologist is indicated for the diagnosis and evaluation of underlying causes of Sweet syndrome (acute febrile neutrophilic dermatosis). An internal medicine specialist may be consulted to evaluate any underlying or triggering conditions.

Prevention

Deterrence is based on avoiding known triggers, such as medications, and treatment of underlying conditions that may be factors.

Long-Term Monitoring

Outpatient care for the skin lesions of Sweet syndrome (acute febrile neutrophilic dermatosis) is usually coordinated by a dermatologist in conjunction with other physicians who may be involved if other underlying diseases are present.

 

Medication

Medication Summary

The goals of pharmacotherapy in Sweet syndrome (acute febrile neutrophilic dermatosis) are to reduce morbidity and to prevent complications. The best-documented first-line options are systemic corticosteroids or topical steroids if the lesions are limited. If the use of corticosteroids is contraindicated, anti-inflammatories such as dapsone or colchicine can be used as alternative first-line agents.

Corticosteroids

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone (Deltasone)

Prednisone is useful in acute neutrophilic dermatitis because of its anti-inflammatory properties. It must be metabolized to the active metabolite prednisolone for effect. Conversion may be impaired in those with liver disease.

Anti-inflammatories

Class Summary

These agents modulate events leading to inflammatory reactions.

Dapsone (Avlosulfon)

Dapsone is bactericidal and bacteriostatic against mycobacteria; its mechanism of action is similar to that of sulfonamides for which competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.

Colchicine

Colchicine decreases leukocyte motility and phagocytosis in inflammatory responses. It has effects against neutrophils, which are probably involved in the expression of cutaneous vasculitis; it has been demonstrated to be steroid sparing in open-label studies. The only double-blinded placebo-controlled trial failed to demonstrate its efficacy; however, several methodological errors occurred in this study. It is not FDA approved in children.

 

Questions & Answers

Overview

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)?

Presentation

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)?

DDX

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)?

Workup

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)?

Treatment

How is acute febrile neutrophilic dermatosis (Sweet syndrome) treated?

Which medications are used for long-term management of acute febrile neutrophilic dermatosis (Sweet syndrome)?

Which specialist consultations are beneficial to patients with acute febrile neutrophilic dermatosis (Sweet syndrome)?

How is acute febrile neutrophilic dermatosis (Sweet syndrome) prevented?

Who provides long-term monitoring of patients with acute febrile neutrophilic dermatosis (Sweet syndrome)?

Medications

What are the goals of drug treatment for acute febrile neutrophilic dermatosis (Sweet syndrome)?

Which medications in the drug class Anti-inflammatories 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)?