Understanding Drug-Induced Sweet's Syndrome
Sweet's syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory skin condition characterized by the sudden onset of fever and tender, red skin lesions. While many cases are idiopathic (of unknown cause), it can also be associated with underlying conditions like infections or malignancies. A significant subtype, known as drug-induced Sweet's syndrome (DISS), occurs as a direct adverse reaction to certain medications. This variant typically appears one to two weeks after starting a new medication and resolves upon its discontinuation. Recognition of DISS is important to avoid unnecessary treatments and ensure prompt recovery.
The most common pharmaceutical culprits
Granulocyte-Colony Stimulating Factors (G-CSFs)
Granulocyte-colony stimulating factor (G-CSF) and its pegylated version (pegfilgrastim) are the most common medications linked to drug-induced Sweet's syndrome. These drugs are primarily used to stimulate the bone marrow to produce more white blood cells (neutrophils), often to combat neutropenia (low neutrophil count) caused by chemotherapy. The subsequent overproduction and activation of neutrophils are believed to be central to the development of DISS in these patients.
Other high-risk drug classes
Several other classes of medications have also been reliably implicated in causing Sweet's syndrome, based on numerous case reports and studies:
- Antineoplastic (chemotherapy) agents: Beyond G-CSFs, various cancer drugs have been associated with DISS. Examples include:
- All-trans retinoic acid (ATRA)
- Bortezomib
- Imatinib mesylate
- Lenalidomide
- Antibiotics: Several antibiotics have been reported to trigger DISS, especially those that can provoke hypersensitivity reactions. Noteworthy examples include:
- Trimethoprim–sulfamethoxazole
- Minocycline
- Norfloxacin and Ofloxacin
- Immunosuppressants: These medications can alter the immune response, leading to inflammatory reactions. The immunosuppressant azathioprine is a documented cause.
- Nonsteroidal anti-inflammatory drugs (NSAIDs): While less common, certain NSAIDs have been reported. This includes diclofenac and celecoxib.
- Antihypertensives and Diuretics: Some medications used to treat high blood pressure and fluid retention have been linked. Case reports cite hydralazine and furosemide as triggers.
- Others: Other drug classes reported in association with DISS include antiepileptics (e.g., carbamazepine, diazepam), antipsychotics (e.g., clozapine), and certain contraceptives.
Distinguishing Drug-Induced vs. Classic Sweet's Syndrome
While sharing similar clinical features, DISS differs from classic (idiopathic) Sweet's syndrome in several key ways. Understanding these differences can aid in diagnosis and management. The timing of onset, patient characteristics, and treatment response can vary significantly.
| Feature | Drug-Induced Sweet's Syndrome | Classic (Idiopathic) Sweet's Syndrome |
|---|---|---|
| Onset | Abrupt onset, typically within 1–2 weeks of starting the causative drug. | Also abrupt, but not clearly linked to a new medication. |
| Associated Conditions | Triggered by the medication, often in patients undergoing chemotherapy or using G-CSFs. | Often associated with upper respiratory tract infections, gastrointestinal infections, inflammatory bowel disease, or pregnancy. |
| Gender Predominance | No strong gender bias is noted; follows the gender of those taking the medication. | More common in middle-aged women. |
| Recurrence | Recurrence is highly likely upon re-exposure to the offending drug. | Recurrences are common, often triggered by a new infection or flare-up of an underlying condition. |
| Blood Neutrophil Count | Can present with low or normal neutrophil counts, especially if caused by chemotherapy. | Typically presents with an elevated neutrophil count (neutrophilia). |
Pathophysiology and Diagnosis
The exact mechanism for DISS is not fully understood but is believed to involve a dysregulation of cytokines—small proteins that act as messengers in the immune system. It is hypothesized that the drug, or its metabolite, triggers an overactive immune response, leading to a cascade of inflammation and the characteristic skin lesions. The diagnostic criteria proposed by Walker and Cohen are still widely used and emphasize the temporal relationship between drug exposure and the onset of symptoms. Confirming the diagnosis often involves a skin biopsy, which reveals a dense infiltrate of mature neutrophils in the dermis.
Management and Outlook
For DISS, the primary course of treatment is the prompt discontinuation of the suspected medication. Many patients experience spontaneous resolution of their symptoms after the drug is stopped. However, to speed up recovery and manage severe symptoms, systemic corticosteroids like prednisone are considered the first-line treatment. The response is often dramatic and rapid.
For localized lesions, high-potency topical or intralesional corticosteroids may be used. Alternative oral agents, such as dapsone, colchicine, or potassium iodide, may be considered if corticosteroids are contraindicated or ineffective. Unlike some other forms of Sweet's syndrome, DISS generally has a favorable prognosis, with lesions healing without scarring.
Conclusion
Drug-induced Sweet's syndrome is a significant and identifiable cause of this acute inflammatory dermatosis. While G-CSF is the most common trigger, healthcare providers must be aware of the wide range of medications that can cause this reaction, including various antibiotics, chemotherapy agents, and anti-inflammatory drugs. A careful review of a patient's medication history is an essential step in diagnosing DISS. Proper management involves discontinuing the offending drug, which can lead to rapid symptom resolution, often with the support of systemic corticosteroids. For more comprehensive information on this topic, consult the National Center for Biotechnology Information (NCBI) database.
