Acute febrile neutrophilic dermatosis (Sweet syndrome) is a rare inflammatory disorder that affects the skin and may also affect the eyes, muscoloskeletal system and internal organs. The presentation involves the abrupt appearance of erythematous papules, plaques or nodules that are painful and edematous. Patients usually have fever and leukocytosis. It is most common between the ages of 30 to 60, but it may happen at any stage of life.
It can be classified in three subtypes:
- Classical: Not due to drugs or cancer. More often related to infections (usually three weeks after upper respiratory or gastrointestinal), pregnancy or inflammatory bowel disease. Not associated with HIV, tuberculosis, chlamydia, viral hepatitis and autoimmune diseases.
- Malignancy-associated: A common trigger of Sweet syndrome. The hematologic cancers (specially AML) are more likely to cause it than solid tumors.
- Drug induced: Many drugs, such as antibiotics (BACTRIM, quinolones, nitrofurantoin, minocycline), antiepileptics, hydralazine, antineoplastics (bortezomib, imatinib, lenalidomide, topotecan), clozapine, G-CSF, furosemide, azathioprine, NSAIDS (celecoxib, diclofenac), retinoids and contraceptives.
The exact mechanism is unclear. Factors that are believed to contribute are hypersensitivity (due to antigens that stimulate the production of cytokines and neutrophil activation), cytokine deregulation (leading to inflammatory response, such as G-CSF that increases neutrophils. G-CSF levels can be increased in active Sweet’s syndrome) and genetic susceptibility (with some evidence about HLA-B54 in Japanese patients and abnormalities in chromosome 3q in some patients with Sweet syndrome).
Cutaneous: Lesions are more common in the trunk and upper extremities. They can present as papules, plaques and/or nodules that are edematous, tender and inflamed with bright red or purple color, and may have a mamilated surface or a central hue, with some lesions resembling a target. Less common forms of cutaneous Sweet syndrome include the bullous (vesicles and flacid bullae on the plaques), subcutaneous (erythematous nodules with little superficial change) and neutrophilic dermatosis of the dorsal hands (pustular plaques on the dorsal surface of the hands).
Other signs and symptoms: Fever, malaise, headache and body ache (myalgias and arthralgias) may occur. Leukocytosis with neutrophilia and elevated inflammatory markers can be present.
Accomitment of organs other than the skin: The most common extracutaneous manifestations are ocular and musculoeskeletal. Less common sites involved include CNS, heart, kidneys, lungs, spleen and intestines.
For the diagnosis of classic Sweet syndrome the patient needs to fit 2 major criteria + 2 (out of 4) minor criteria):
1. Abrupt onset of painful erythematous plaques or nodules
2. Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
3. Fever >38°C
4. Association w/ underlying malignancy (hematologic or visceral), inflammatory disease or pregnancy, OR preceded by upper respiratory infection, gastrointestinal infection, or vaccination
5. Excellent response to treatment with systemic glucocorticoids or potassium iodide
6. Abnormal laboratory values at presentation (three of four of the following: erythrocyte sedimentation rate >20 mm/hour, positive C-reactive protein, >8000 leukocytes, >70 percent neutrophils)
For drug induced Sweed Syndrome, the patient has to fit all the following:
A. Abrupt onset of painful erythematous plaques or nodules
B. Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
C. Pyrexia >38°C
D. Temporal relationship between drug ingestion and clinical presentation, or temporally-related recurrence after oral challenge
E. Temporally-related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids
As you can see, the biopsy is fundamental for a definitive diagnosis.
Other tests to order: CBC w/differential, CMP, ESR or RCP, Urinalysis and Pregnancy test. Evaluation for malignancy may be considered.
In patients with a small and localized number of lesions, topical or intralesional steroids can be used. However, systemic agents are the first-line of treatment.
Corticosteroids such as Prednisone can be used: 1mg/kg/day as a single morning dose. Some patients may require 2 to 3 months of treatment (remember to taper before suspending). Other first-line agents include potassium iodide and colchicine.
Second-line agents include indomethacin, clofazimine, cyclosporin and dapsone.
SOURCES & FURTHER READING:
- Sweet’s syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis. Philip R Cohen. Cohen; licensee BioMed Central Ltd. 2007. Received: 05 July 2007Accepted: 26 July 2007Published: 26 July 2007.
- Sweet syndrome: Clinical presentation, associations, and response to treatment in 77 patients. Nicole M. Rochet et al. Journal of the American Academy of Dermatology Volume 69, Issue 4, October 2013, Pages 557–564.
- Autoinflammatory Skin Disorders in Inflammatory Bowel Diseases, Pyoderma Gangrenosum and Sweet’s Syndrome: a Comprehensive Review and Disease Classification Criteria. Angelo V. Marzano et al. Clinical Reviews in Allergy & Immunology, October 2013, Volume 45, Issue 2, pp 202-210.
- Efficacy of Anti-Interleukin-1 Receptor Antagonist Anakinra (Kineret®) in a Case of Refractory Sweet’s Syndrome. Kluger N et al. Dermatology 2011;222:123–127.