Sweet’s SyndromeSweet’s Syndrome

Allison DupontAllison Dupont

AM ReportAM Report

1/17/061/17/06

DefinitionDefinition

Sweet’s syndrome (acute febrile Sweet’s syndrome (acute febrile neutrophilic dermatosis) is neutrophilic dermatosis) is characterized by:characterized by: FeverFever Peripheral neutrophiliaPeripheral neutrophilia Painful red skin papules, nodules and/or Painful red skin papules, nodules and/or

plaquesplaques Neutrophilic infiltration of skin Neutrophilic infiltration of skin

(particularly the dermis)(particularly the dermis)

Clinical PresentationClinical Presentation

FeverFever (>38 (>38˚C) can be intermittent and may ˚C) can be intermittent and may precede skin manifestations by days to weeks.precede skin manifestations by days to weeks.

Systemic symptomsSystemic symptoms may include headache, may include headache, myalgia, arthralgia, and general malaise.myalgia, arthralgia, and general malaise.

Cutaneous lesionsCutaneous lesions consist of erythematous to consist of erythematous to violaceous tender papules which may coalesce to violaceous tender papules which may coalesce to form plaques.form plaques. The plaques are not pruritic.The plaques are not pruritic. Most often found on the face, neck and upper extremities Most often found on the face, neck and upper extremities

(especially the dorsum of the hands), but can occur (especially the dorsum of the hands), but can occur anywhere.anywhere.

Lesions on the lower extremities may resemble erythema Lesions on the lower extremities may resemble erythema nodosum.nodosum.

Clinical PresentationClinical Presentation

Oral ulcersOral ulcers (more common in (more common in patients with Sweet’s syndrome and patients with Sweet’s syndrome and a hematologic malignancy.a hematologic malignancy.

Ocular involvementOcular involvement (uncommon in (uncommon in malignancy-associated and drug-malignancy-associated and drug-induced Sweet’s syndrome).induced Sweet’s syndrome). Conjunctivitis, episcleritisConjunctivitis, episcleritis

Clinical PresentationClinical Presentation

Involvement of internal organs may Involvement of internal organs may occur leading to:occur leading to: AlveolitisAlveolitis Sterile osteomyelitisSterile osteomyelitis Involvement of liver, pancreas, and/or Involvement of liver, pancreas, and/or

kidneyskidneys Neurologic and psychiatric changesNeurologic and psychiatric changes

Laboratory FindingsLaboratory Findings

Lab findings are nonspecific.Lab findings are nonspecific. Majority will have peripheral neutrophilia.Majority will have peripheral neutrophilia. Other possible lab abnormalities include:Other possible lab abnormalities include:

Elevated sedimentation rateElevated sedimentation rate Elevated C-reactive proteinElevated C-reactive protein LeukocytosisLeukocytosis

Consider evaluation of hepatic and renal Consider evaluation of hepatic and renal function.function.

PathologyPathology

Sweet’s syndrome characteristically Sweet’s syndrome characteristically involves dense neutrophilic infiltration involves dense neutrophilic infiltration of the dermis +/- dermal edema.of the dermis +/- dermal edema.

Neutrophil karyorrhexis is commonly Neutrophil karyorrhexis is commonly seen.seen.

There is no involvement of the There is no involvement of the vasculature of the skin and no necrosis vasculature of the skin and no necrosis (in contast to pyoderma gangrenosum).(in contast to pyoderma gangrenosum).

DiagnosisDiagnosis

Major CriteriaMajor Criteria

Abrupt onset of painful Abrupt onset of painful erythematous plaques or nodules.erythematous plaques or nodules.

Histopathologic evidence of a Histopathologic evidence of a dense dermal neutrophilic dense dermal neutrophilic infiltrate infiltrate without vasculitiswithout vasculitis..

Minor CriteriaMinor Criteria

Fever (>38Fever (>38˚C)˚C)

Association with an underlying Association with an underlying hematological/visceral hematological/visceral malignancy, inflammatory malignancy, inflammatory disease, or pregnancy disease, or pregnancy oror preceded by an upper respiratory preceded by an upper respiratory or GI infection or vaccination.or GI infection or vaccination.

Excellent response to treatment Excellent response to treatment with systemic corticosteroids.with systemic corticosteroids.

Peripheral neutrophilia (>70% Peripheral neutrophilia (>70% neutrophils)neutrophils)

Associated ConditionsAssociated Conditions

Sweet’s syndrome is associated with an Sweet’s syndrome is associated with an underlying disease or condition in up to underlying disease or condition in up to 50% of patients.50% of patients.

Sweet’s syndrome may be the presenting Sweet’s syndrome may be the presenting sign and the underlying disease may not sign and the underlying disease may not become apparent for several years after become apparent for several years after Sweet’s syndrome occurs.Sweet’s syndrome occurs.

There is a female predominance except in There is a female predominance except in the case of malignancy-associated Sweet’s the case of malignancy-associated Sweet’s syndrome.syndrome.

Associated ConditionsAssociated Conditions

1.1. MalignancyMalignancy Approximately 21% of patients with Sweet’s Approximately 21% of patients with Sweet’s

syndrome have a malignancy.syndrome have a malignancy. 15% hematological (most commonly AML)15% hematological (most commonly AML) 6% solid tumors (most commonly 6% solid tumors (most commonly

carcinomas of the GU tract, GI tract, or carcinomas of the GU tract, GI tract, or breast)breast)

2.2. InfectionsInfections Mostly of the upper respiratory or GI tractMostly of the upper respiratory or GI tract Streptococcus, mycobacterium, Yersinia, Streptococcus, mycobacterium, Yersinia,

Salmonella, ShigellaSalmonella, Shigella

Associated ConditionsAssociated Conditions

3.3. Inflammatory bowel diseaseInflammatory bowel disease Sweet’s syndrome may occur alone or in Sweet’s syndrome may occur alone or in

combination with pyoderma gangrenosum.combination with pyoderma gangrenosum.

4.4. PregnancyPregnancy

5.5. Other conditions with a possible Other conditions with a possible association:association:

-Sarcoidosis-Sarcoidosis

-Rheumatoid arthritis-Rheumatoid arthritis

-Thyroid disease (Grave’s-Thyroid disease (Grave’s disease and Hashimoto’s disease and Hashimoto’s thyroiditis)thyroiditis)

Drug-induced Sweet’s Drug-induced Sweet’s syndromesyndrome

Criteria slightly different than Criteria slightly different than classical syndrome.classical syndrome.

Temporal relationship between drug Temporal relationship between drug ingestion/injection and clinical ingestion/injection and clinical presentation.presentation.

Resolution of lesions/symptoms after Resolution of lesions/symptoms after withdrawal of drug or treatment withdrawal of drug or treatment with corticosteroids.with corticosteroids.

Drug-induced Sweet’s Drug-induced Sweet’s syndromesyndrome

G-CSF is responsible for the majority G-CSF is responsible for the majority of cases.of cases.

Other possible causes: furosemide, Other possible causes: furosemide, lithium, hydralazine, trimethoprim-lithium, hydralazine, trimethoprim-sulfamethoxazole, and oral sulfamethoxazole, and oral contraceptives.contraceptives.

PathogenesisPathogenesis

Etiology of Sweet’s syndrome is Etiology of Sweet’s syndrome is unknown.unknown.

Presumed to be due to a hypersensitivity Presumed to be due to a hypersensitivity reaction to an eliciting antigen which reaction to an eliciting antigen which leads to stimulation of cytokine release.leads to stimulation of cytokine release.

Cytokines precipitate neutrophil Cytokines precipitate neutrophil activation and infiltration.activation and infiltration.

Response to treatment with Response to treatment with corticosteroids supports this etiology.corticosteroids supports this etiology.

PathogenesisPathogenesis

The source of the eliciting antigen The source of the eliciting antigen may be diverse, including bacterial, may be diverse, including bacterial, viral or tumoral antigens.viral or tumoral antigens.

TreatmentTreatment

Gold standard: Gold standard: Systemic Systemic corticosteroidscorticosteroids Start at 1 mg/kg/day prednisone with long Start at 1 mg/kg/day prednisone with long

taper (4-6 weeks) to 10 mg/day.taper (4-6 weeks) to 10 mg/day. Many patients require several months of Many patients require several months of

10-30 mg/day to suppress recurrences.10-30 mg/day to suppress recurrences. Localized Sweet’s syndrome can Localized Sweet’s syndrome can

sometimes be treated with high-potency sometimes be treated with high-potency topical corticosteroidstopical corticosteroids..

TreatmentTreatment

Other first-line agents include:Other first-line agents include:

1.1. Oral potassium iodideOral potassium iodide-Systemic symptoms resolve in 1-2 days.-Systemic symptoms resolve in 1-2 days.

-Dermatitis resolves in 3-5 days.-Dermatitis resolves in 3-5 days.

2.2. ColchicineColchicine-Systemic symptoms resolve in 2-3 days.-Systemic symptoms resolve in 2-3 days.

-Dermatitis resolves in 2-5 days.-Dermatitis resolves in 2-5 days.

Alternative therapiesAlternative therapies

IndomethacinIndomethacin ClofazimineClofazimine CyclosporineCyclosporine DapsoneDapsone

ReferencesReferences

Burall, Barbara M.D. “Sweet’s syndrome (acute febrile neutrophilic dermatosis)”. Burall, Barbara M.D. “Sweet’s syndrome (acute febrile neutrophilic dermatosis)”. Dermatology Online JournalDermatology Online Journal 5(1):8. 5(1):8.

Cohen, Philip R. MD, Kurzrock, Razelle MD. “Sweet’s syndrome revisited: a review of Cohen, Philip R. MD, Kurzrock, Razelle MD. “Sweet’s syndrome revisited: a review of disease concepts”. disease concepts”. International Journal of DermatologyInternational Journal of Dermatology. Volume 42, Issue 10. . Volume 42, Issue 10. October 2003.October 2003.

Cohen, Philip R. “Sweet’s syndrome”. Cohen, Philip R. “Sweet’s syndrome”. OrphanetOrphanet. October. October2003.2003.

Federman et al. “Cutaneous manifestations of malignancy”. Federman et al. “Cutaneous manifestations of malignancy”. Postgraduate Medicine Postgraduate Medicine OnlineOnline. January 2005.. January 2005.

Joe, Edwin K. MD. “Sweet’s syndrome”. Joe, Edwin K. MD. “Sweet’s syndrome”. Dermatology Online JournalDermatology Online Journal 9(4):28. 9(4):28.

Moschella, Samuel L. MD. “Neutrophilic dermatoses”. Moschella, Samuel L. MD. “Neutrophilic dermatoses”. UpToDateUpToDate. .

““Sweet’s Syndrome”. Sweet’s Syndrome”. Dermis.netDermis.net..