Sweet Syndrome: Symptoms, Types, Causes and Treatment

Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare and intriguing skin condition that can appear suddenly and cause significant discomfort. Despite its distinctive presentation, Sweet syndrome remains underrecognized and often misunderstood due to its varied manifestations and associations with systemic diseases. In this comprehensive article, we'll explore the symptoms, types, causes, and treatment options for Sweet syndrome, synthesizing up-to-date knowledge from clinical research to provide a clear, detailed overview for patients, caregivers, and medical professionals alike.

Symptoms of Sweet Syndrome

Sweet syndrome is notorious for its dramatic and rapid onset of symptoms, often leaving patients and clinicians searching for answers. Recognizing the key clinical features is vital for timely diagnosis and management.

Symptom	Description	Common Sites	Source(s)
Skin lesions	Tender, erythematous papules, nodules, plaques, or pustules	Face, neck, limbs	1 2 3 5
Fever	Sudden onset, often high-grade	Systemic	1 2 5
Arthralgia	Joint pain, sometimes with swelling	Various joints	5 6
Systemic signs	Headache, malaise, fatigue, oral/genital lesions	Variable	5 10
Ocular signs	Conjunctivitis, episcleritis, iritis, periorbital inflammation	Eyes	8
Laboratory	Neutrophilia, elevated ESR/CRP, sometimes leukopenia/anemia	Blood	1 4 6 9

Table 1: Key Symptoms

Common Skin and Systemic Manifestations

The hallmark of Sweet syndrome is the abrupt appearance of painful, red to purple skin lesions. These typically manifest as papules, nodules, plaques, or occasionally pustules. The lesions are often tender to the touch, sometimes accompanied by swelling, and frequently appear on the face, neck, upper trunk, and upper limbs, though they can also involve the hands and lower limbs. In some cases, oral or genital mucosal lesions may also occur 1 2 3 5.

Systemic symptoms such as high-grade fever are present in most cases, making Sweet syndrome one of the prototypical febrile dermatoses. Patients might also experience headaches, general malaise, and profound fatigue. Arthralgia, or pain in the joints, is commonly reported and can add to the overall discomfort and functional impairment 5 6.

Ocular Involvement

While less common, Sweet syndrome can also affect the eyes. Ocular signs may include conjunctivitis, episcleritis, scleritis, periorbital swelling, and, in severe cases, iritis or peripheral ulcerative keratitis. These manifestations generally occur alongside the skin lesions and often improve with systemic steroid therapy 8.

Laboratory Findings

Laboratory assessments typically reveal systemic inflammation. Elevated white blood cell counts (neutrophilia), increased erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are characteristic findings. However, patients with malignancy-associated Sweet syndrome may instead present with leukopenia, anemia, or thrombocytopenia, reflecting the underlying hematologic disorder 1 4 6 9.

Types of Sweet Syndrome

Sweet syndrome is not a singular disease but a spectrum of related disorders, each with unique associations and implications. Understanding its subtypes is crucial for diagnosis and guiding further investigations.

Type	Defining Features	Typical Demographics or Associations	Source(s)
Classic	Idiopathic, may follow infection, IBD, or pregnancy	Women aged 30–50; often post-infection	1 2 3 5
Malignancy-Associated	Paraneoplastic; co-occurs with or signals malignancy	Hematologic cancers (AML, MDS), solid tumors	1 6 9 10
Drug-Induced	Triggered by medications (e.g., G-CSF, azathioprine, antibiotics)	Any age; often recent drug exposure	1 2 4 6

Table 2: Types of Sweet Syndrome

Classic (Idiopathic) Sweet Syndrome

Classic Sweet syndrome (CSS) refers to cases with no clear underlying malignancy or drug trigger. It often affects women between the ages of 30 and 50 and may be preceded by an upper respiratory tract infection, gastrointestinal infection, inflammatory bowel disease, or pregnancy 1 2 3 5. Recurrence is seen in about one-third of these patients 1.

Malignancy-Associated Sweet Syndrome (MASS)

This subtype is a paraneoplastic phenomenon, most commonly linked to hematologic cancers like acute myelogenous leukemia (AML) and myelodysplastic syndromes, but can also be associated with solid tumors 1 6 9 10. Sweet syndrome may precede, coincide with, or follow the diagnosis of cancer—sometimes serving as the first sign of an undiagnosed malignancy or relapse 1 9.

Drug-Induced Sweet Syndrome (DISS)

Drug-induced Sweet syndrome is triggered by medications, with granulocyte-colony stimulating factor (G-CSF) being the most common culprit 1 2 4 6. Other drugs linked to Sweet syndrome include antibiotics (minocycline, nitrofurantoin), azathioprine, antiepileptics, antihypertensives, oral contraceptives, and retinoids. Discontinuing the offending drug usually leads to rapid improvement 4.

Causes of Sweet Syndrome

The causes of Sweet syndrome are multifactorial and complex, involving an interplay of immune dysregulation, hypersensitivity reactions, and, in some cases, genetic predisposition.

Cause Category	Examples/Triggers	Notes	Source(s)
Infections	Upper respiratory tract, GI infections	Often precede CSS	1 2 3 5
Systemic Disease	Malignancy (esp. AML, MDS), IBD, pregnancy	MASS can be harbinger of cancer	1 6 9 10
Drugs	G-CSF, azathioprine, antibiotics, antiepileptics	Drug discontinuation is key	1 2 4 6
Immune Response	Cytokine-mediated neutrophil infiltration	Pathogenesis not fully understood	1 2 3 7 11
Genetics	Familial cases, gene variants (rare)	Under investigation	7

Table 3: Causes and Triggers

Infections

A significant proportion of classic Sweet syndrome cases are preceded by infections, particularly of the upper respiratory or gastrointestinal tract. The syndrome is thought to be a hypersensitivity reaction to infectious or inflammatory stimuli, with cytokines playing a central role in orchestrating neutrophil recruitment to the skin 1 2 3 5.

Systemic Diseases and Malignancy

Malignancy-associated Sweet syndrome is most frequently linked to hematologic cancers, especially AML and myelodysplastic syndromes, but can also occur with solid tumors and, less often, in association with inflammatory bowel disease or pregnancy 1 6 9 10. The cutaneous eruption may signal the presence or recurrence of cancer, making thorough evaluation essential in unexplained cases.

Drug Triggers

Numerous medications have been implicated in drug-induced Sweet syndrome. G-CSF is the most common, but others such as azathioprine (notably leading to neutropenia in affected patients), certain antibiotics, antiepileptics, and oral contraceptives have also been reported as triggers 1 2 4 6. Drug-induced cases typically resolve upon cessation of the culprit medication 4.

Immune Dysregulation and Cytokine Storm

The exact pathogenesis remains elusive, but there is growing evidence that Sweet syndrome is a cytokine-mediated process, characterized by excessive neutrophil activation and infiltration of the skin. Interleukin-1 (IL-1), IL-6, and other pro-inflammatory mediators are thought to play key roles 1 2 3 7 11.

Genetic Factors

Genetic predisposition is being studied, with rare familial cases and associations with specific gene variants reported. However, these are not yet well defined and account for a minority of cases 7.

Treatment of Sweet Syndrome

Once diagnosed, Sweet syndrome is highly responsive to appropriate therapy. Swift management not only relieves symptoms but can also prevent complications and guide investigation of underlying causes.

Treatment	Use Case/Indication	Notes/Effectiveness	Source(s)
Systemic Steroids	First-line for most cases	Rapid symptom resolution	1 2 3 5 10
Topical/Intralesional Steroids	Localized lesions	For mild/limited disease	1 5
Potassium Iodide	Oral, first-line alternative	Used if steroids contraind.	1 2 3
Colchicine	Oral, first-line alternative	Especially in mild disease	1 2 3
NSAIDs (Indomethacin)	Second-line or adjunctive	For refractory cases	1 2 3
Immunosuppressants	Cyclosporine, dapsone, clofazimine	Severe/refractory disease	1 3 5 8
Treat Underlying Cause	Cancer, infection, drug withdrawal	Essential for long-term control	1 4 6 9 10

Table 4: Treatment Approaches

Systemic Corticosteroids

Systemic corticosteroids are the gold standard and first-line therapy for Sweet syndrome 1 2 3 5 10. They induce a rapid and dramatic response—fever and pain typically improve within 24–48 hours, and skin lesions clear within a week. Prednisone is commonly used, with gradual tapering over weeks to avoid relapse.

Topical and Intralesional Steroids

For localized or limited disease, high-potency topical corticosteroids or intralesional injections may suffice, providing symptomatic relief without systemic side effects 1 5.

Steroid-Sparing and Alternative Agents

For patients who cannot tolerate corticosteroids or have refractory disease, alternatives include:

• Potassium iodide and colchicine (first-line oral alternatives) 1 2 3
• NSAIDs such as indomethacin (second-line) 1 2 3
• Immunosuppressants (cyclosporine, dapsone, clofazimine) for severe, relapsing, or steroid-resistant cases 1 3 5

Addressing the Underlying Cause

In malignancy-associated or drug-induced cases, treating the underlying cancer or discontinuing the offending drug is essential for long-term resolution. Some patients may require oncologic therapy in addition to steroids for complete remission 1 4 6 9 10.

Prognosis and Monitoring

Most patients experience complete resolution with appropriate therapy. However, recurrence is not uncommon, particularly in classic and malignancy-associated forms. Ongoing monitoring for relapse and vigilance for underlying malignancy are advised, especially in patients with laboratory abnormalities such as anemia or leukopenia 1 6 9 10.

Conclusion

Sweet syndrome, while rare, is a distinctive and often dramatic dermatological condition with important systemic associations. Recognizing its features and underlying triggers is essential for effective management and optimal patient outcomes.

Key points covered:

• Symptoms: Rapid onset of painful red skin lesions, fever, joint pain, and occasionally ocular or mucosal involvement 1 2 3 5 8.
• Types: Classified as classic (idiopathic), malignancy-associated, and drug-induced, each with unique associations and implications 1 2 3 5 6.
• Causes: Multifactorial, involving infections, systemic diseases (notably hematologic malignancies), drug triggers, and immune dysregulation 1 2 3 4 6 7 9 10.
• Treatment: Prompt systemic corticosteroid therapy is highly effective; alternatives and steroid-sparing agents are available for specific cases. Managing underlying causes is crucial to prevent recurrence 1 2 3 4 5 6 9 10.

For patients and clinicians alike, awareness and early recognition of Sweet syndrome can dramatically improve outcomes and, in some cases, uncover life-threatening underlying conditions.