Sweet’s Syndrome Allison Dupont AM Report 1/17/06

Definition Sweet’s syndrome (acute febrile neutrophilic dermatosis) is characterized by: Sweet’s syndrome (acute febrile neutrophilic dermatosis) is characterized by: Fever Fever Peripheral neutrophilia Peripheral neutrophilia Painful red skin papules, nodules and/or plaques Painful red skin papules, nodules and/or plaques Neutrophilic infiltration of skin (particularly the dermis) Neutrophilic infiltration of skin (particularly the dermis)

Clinical Presentation Fever (>38˚C) can be intermittent and may precede skin manifestations by days to weeks. Fever (>38˚C) can be intermittent and may precede skin manifestations by days to weeks. Systemic symptoms may include headache, myalgia, arthralgia, and general malaise. Systemic symptoms may include headache, myalgia, arthralgia, and general malaise. Cutaneous lesions consist of erythematous to violaceous tender papules which may coalesce to form plaques. Cutaneous lesions consist of erythematous to violaceous tender papules which may coalesce to form plaques. The plaques are not pruritic. The plaques are not pruritic. Most often found on the face, neck and upper extremities (especially the dorsum of the hands), but can occur anywhere. Most often found on the face, neck and upper extremities (especially the dorsum of the hands), but can occur anywhere. Lesions on the lower extremities may resemble erythema nodosum. Lesions on the lower extremities may resemble erythema nodosum.

Clinical Presentation Oral ulcers (more common in patients with Sweet’s syndrome and a hematologic malignancy. Oral ulcers (more common in patients with Sweet’s syndrome and a hematologic malignancy. Ocular involvement (uncommon in malignancy-associated and drug-induced Sweet’s syndrome). Ocular involvement (uncommon in malignancy-associated and drug-induced Sweet’s syndrome). Conjunctivitis, episcleritis Conjunctivitis, episcleritis

Clinical Presentation Involvement of internal organs may occur leading to: Involvement of internal organs may occur leading to: Alveolitis Alveolitis Sterile osteomyelitis Sterile osteomyelitis Involvement of liver, pancreas, and/or kidneys Involvement of liver, pancreas, and/or kidneys Neurologic and psychiatric changes Neurologic and psychiatric changes

Laboratory 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 rate Elevated sedimentation rate Elevated C-reactive protein Elevated C-reactive protein Leukocytosis Leukocytosis Consider evaluation of hepatic and renal function. Consider evaluation of hepatic and renal function.

Pathology Sweet’s syndrome characteristically involves dense neutrophilic infiltration of the dermis +/- dermal edema. Sweet’s syndrome characteristically involves dense neutrophilic infiltration of the dermis +/- dermal edema. Neutrophil karyorrhexis is commonly seen. Neutrophil karyorrhexis is commonly seen. There is no involvement of the vasculature of the skin and no necrosis (in contast to pyoderma gangrenosum). There is no involvement of the vasculature of the skin and no necrosis (in contast to pyoderma gangrenosum).

Diagnosis Major Criteria Abrupt onset of painful erythematous plaques or nodules. Abrupt onset of painful erythematous plaques or nodules. Histopathologic evidence of a dense dermal neutrophilic infiltrate without vasculitis. Histopathologic evidence of a dense dermal neutrophilic infiltrate without vasculitis. Minor Criteria Fever (>38˚C) Fever (>38˚C) Association with an underlying hematological/visceral malignancy, inflammatory disease, or pregnancy or preceded by an upper respiratory or GI infection or vaccination. Association with an underlying hematological/visceral malignancy, inflammatory disease, or pregnancy or preceded by an upper respiratory or GI infection or vaccination. Excellent response to treatment with systemic corticosteroids. Excellent response to treatment with systemic corticosteroids. Peripheral neutrophilia (>70% neutrophils) Peripheral neutrophilia (>70% neutrophils)

Associated Conditions Sweet’s syndrome is associated with an underlying disease or condition in up to 50% of patients. Sweet’s syndrome is associated with an underlying disease or condition in up to 50% of patients. Sweet’s syndrome may be the presenting sign and the underlying disease may not become apparent for several years after Sweet’s syndrome occurs. Sweet’s syndrome may be the presenting sign and the underlying disease may not become apparent for several years after Sweet’s syndrome occurs. There is a female predominance except in the case of malignancy-associated Sweet’s syndrome. There is a female predominance except in the case of malignancy-associated Sweet’s syndrome.

Associated Conditions 1. Malignancy Approximately 21% of patients with Sweet’s syndrome have a malignancy. Approximately 21% of patients with Sweet’s syndrome have a malignancy. 15% hematological (most commonly AML) 15% hematological (most commonly AML) 6% solid tumors (most commonly carcinomas of the GU tract, GI tract, or breast) 6% solid tumors (most commonly carcinomas of the GU tract, GI tract, or breast) 2. Infections Mostly of the upper respiratory or GI tract Mostly of the upper respiratory or GI tract Streptococcus, mycobacterium, Yersinia, Salmonella, Shigella Streptococcus, mycobacterium, Yersinia, Salmonella, Shigella

Associated Conditions 3. Inflammatory bowel disease Sweet’s syndrome may occur alone or in combination with pyoderma gangrenosum. Sweet’s syndrome may occur alone or in combination with pyoderma gangrenosum. 4. Pregnancy 5. Other conditions with a possible association: -Sarcoidosis -Rheumatoid arthritis -Thyroid disease (Grave’s disease and Hashimoto’s thyroiditis)

Drug-induced Sweet’s syndrome Criteria slightly different than classical syndrome. Criteria slightly different than classical syndrome. Temporal relationship between drug ingestion/injection and clinical presentation. Temporal relationship between drug ingestion/injection and clinical presentation. Resolution of lesions/symptoms after withdrawal of drug or treatment with corticosteroids. Resolution of lesions/symptoms after withdrawal of drug or treatment with corticosteroids.

Drug-induced Sweet’s syndrome G-CSF is responsible for the majority of cases. G-CSF is responsible for the majority of cases. Other possible causes: furosemide, lithium, hydralazine, trimethoprim- sulfamethoxazole, and oral contraceptives. Other possible causes: furosemide, lithium, hydralazine, trimethoprim- sulfamethoxazole, and oral contraceptives.

Pathogenesis Etiology of Sweet’s syndrome is unknown. Etiology of Sweet’s syndrome is unknown. Presumed to be due to a hypersensitivity reaction to an eliciting antigen which leads to stimulation of cytokine release. Presumed to be due to a hypersensitivity reaction to an eliciting antigen which leads to stimulation of cytokine release. Cytokines precipitate neutrophil activation and infiltration. Cytokines precipitate neutrophil activation and infiltration. Response to treatment with corticosteroids supports this etiology. Response to treatment with corticosteroids supports this etiology.

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

Treatment Gold standard: Systemic corticosteroids Gold standard: Systemic corticosteroids Start at 1 mg/kg/day prednisone with long taper (4-6 weeks) to 10 mg/day. Start at 1 mg/kg/day prednisone with long taper (4-6 weeks) to 10 mg/day. Many patients require several months of Many patients require several months of mg/day to suppress recurrences mg/day to suppress recurrences. Localized Sweet’s syndrome can sometimes be treated with high-potency topical corticosteroids. Localized Sweet’s syndrome can sometimes be treated with high-potency topical corticosteroids.

Treatment Other first-line agents include: 1. Oral potassium iodide -Systemic symptoms resolve in 1-2 days. -Dermatitis resolves in 3-5 days. 2. Colchicine -Systemic symptoms resolve in 2-3 days. -Dermatitis resolves in 2-5 days.

Alternative therapies Indomethacin Indomethacin Clofazimine Clofazimine Cyclosporine Cyclosporine Dapsone Dapsone

References Burall, Barbara M.D. “Sweet’s syndrome (acute febrile neutrophilic dermatosis)”. Dermatology Online Journal 5(1):8. Cohen, Philip R. MD, Kurzrock, Razelle MD. “Sweet’s syndrome revisited: a review of disease concepts”. International Journal of Dermatology. Volume 42, Issue 10. October Cohen, Philip R. “Sweet’s syndrome”. Orphanet. October Federman et al. “Cutaneous manifestations of malignancy”. Postgraduate Medicine Online. January Joe, Edwin K. MD. “Sweet’s syndrome”. Dermatology Online Journal 9(4):28. Moschella, Samuel L. MD. “Neutrophilic dermatoses”. UpToDate. “Sweet’s Syndrome”. Dermis.net.