Sweet syndrome
Acute febrile neutrophilic dermatosis; "Gomm-Button disease" (older eponym); Sweet's syndrome
Sweet syndrome — formally "acute febrile neutrophilic dermatosis" since the original description by Robert Douglas Sweet in 1964 — is a neutrophilic dermatosis characterised clinically by abrupt-onset fever, painful tender erythematous to violaceous plaques and nodules (frequently mistaken for cellulitis), peripheral neutrophilia, and histologically by a dense neutrophilic infiltrate of the upper dermis without leukocytoclastic vasculitis. Three clinical settings are recognised — classical / idiopathic Sweet syndrome (often post-infective, particularly streptococcal upper respiratory or yersinial enteric infection), drug-induced Sweet syndrome (most commonly G-CSF, all-trans retinoic acid, hydralazine, BRAF / MEK inhibitors, anti-PD-1, sulfonamides), and paraneoplastic ("malignancy-associated") Sweet syndrome — accounting for ~20% of cases and most strongly associated with acute myeloid leukaemia and myelodysplastic syndrome (~85% of paraneoplastic cases), with smaller contributions from lymphoproliferative malignancy and solid tumours (breast, GU, GI). Paraneoplastic Sweet syndrome may precede the diagnosis of the underlying malignancy by months to years, providing a major diagnostic opportunity for early haematological cancer detection.
Clinical features
- Abrupt-onset fever (often >38 °C) — typically precedes the eruption by hours to days.
- Cutaneous:
- Painful, tender, well-demarcated, juicy / oedematous erythematous to violaceous plaques and nodules — "pseudovesicular" appearance from extreme oedema.
- Coalescent plaques up to several cm.
- Distribution — face, neck, upper trunk, dorsal hands, extensor extremities; asymmetric.
- Frequently mistaken for cellulitis (which it is not).
- Targetoid or annular variants.
- "Pathergy" — new lesions develop at sites of trauma / venepuncture.
- Systemic features — malaise, arthralgia, myalgia, headache, sterile peripheral neutrophilia.
- Extracutaneous Sweet syndrome — sterile neutrophilic infiltration of the eye (conjunctivitis, episcleritis, iritis, ulcer), mouth, lungs, kidneys, CNS, bone, joints, liver, heart.
- Median age 40–60; F>M slightly (idiopathic); M>F in malignancy-associated.
Three clinical contexts
- Classical / idiopathic (~70%) — preceded by upper respiratory tract infection (streptococcal), yersinial enteric infection, IBD flare, pregnancy. Female-predominant. Responds rapidly to corticosteroid.
- Drug-induced (~10%):
- G-CSF (filgrastim, pegfilgrastim) — the commonest single cause.
- All-trans retinoic acid (ATRA) — particularly during AML differentiation syndrome.
- BRAF inhibitor (vemurafenib, dabrafenib).
- Anti-PD-1 immunotherapy.
- Hydralazine.
- Sulfonamides, minocycline.
- Resolves on drug withdrawal.
- Paraneoplastic (~20%):
- Acute myeloid leukaemia and myelodysplastic syndrome — the large majority of paraneoplastic cases.
- Lymphoproliferative malignancy — chronic myeloid leukaemia, chronic lymphocytic leukaemia, multiple myeloma, lymphoma.
- Solid tumours — genitourinary (urothelial), breast, GI, ovarian, lung.
- Paraneoplastic Sweet may precede the cancer diagnosis by months to years.
- "Histiocytoid Sweet syndrome" — a histopathological variant strongly associated with myelodysplastic syndrome.
Diagnostic criteria (modified Su & Liu)
Both major + 2 of 4 minor criteria:
- Major:
- Abrupt onset of typical cutaneous lesions.
- Histopathology consistent with Sweet syndrome (dense neutrophilic infiltrate without leukocytoclastic vasculitis).
- Minor:
- Fever >38 °C.
- Association with underlying haematological / visceral malignancy, inflammatory disease or pregnancy, OR preceded by upper respiratory tract / GI infection or vaccination.
- Excellent response to systemic corticosteroid or potassium iodide.
- Abnormal laboratory values at presentation (3 of 4): ESR >20, raised CRP, WCC >8, neutrophils >70%.
Cancer workup in newly diagnosed Sweet
- FBC with peripheral blood film and flow cytometry — particularly to identify circulating blasts / dysplasia.
- U&E, LFT, LDH, calcium, ferritin.
- Bone marrow biopsy if cytopenias, atypical cells, or persistent / recurrent Sweet syndrome.
- Cytogenetics for AML / MDS panel.
- CT chest/abdomen/pelvis ± PET-CT for solid-tumour screening.
- Tumour markers as indicated by symptoms.
- Refer to haematology MDT if any abnormality.
- Prolonged surveillance — paraneoplastic Sweet may precede cancer diagnosis by years.
Management
- First-line:
- Systemic corticosteroid — prednisolone 0.5–1 mg/kg/day with rapid taper over 4–6 weeks; classical Sweet typically responds dramatically within 24–48 hours.
- Topical / intralesional corticosteroids for localised disease.
- Steroid-sparing for recurrent / refractory disease:
- Colchicine.
- Dapsone.
- Potassium iodide.
- Methotrexate, cyclosporine, mycophenolate.
- TNF inhibitors (infliximab, etanercept, adalimumab).
- JAK inhibitors (tofacitinib, baricitinib).
- Anakinra (IL-1 antagonist).
- Treat underlying triggers — withdraw causative drug; treat underlying malignancy; treat associated infection.
- Counsel about drug avoidance (especially sulfonamides, hydralazine in patients with prior drug-induced Sweet syndrome).
- Long-term surveillance for cancer in paraneoplastic Sweet syndrome.
References
- Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol; 1964.
- Heath MS, Ortega-Loayza AG. Insights into the pathogenesis of Sweet syndrome. Front Immunol; 2019.
- Cohen PR, Kurzrock R. Sweet's syndrome — a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis; 2007.
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