Sweet syndrome (Diagnosis, Management)

 

DIAGNOSIS OF SWEET SYNDROME

Diagnosis is based on symptoms and tissue samples (biopsy). A key feature of Sweet Syndrome is that the skin lesions heal without scarring, and there’s no blood vessel inflammation in the tissue samples. This is important because it might indicate other serious illnesses, like cancer, and early diagnosis and treatment are critical.

CLASSIC OR IDIOPATHIC SWEET SYNDROME:

To diagnose this, both "major criteria" and at least two "minor criteria" need to be met.

Major Criteria:

  1. Sudden onset of painful red bumps or lumps, sometimes with blisters or other skin changes.

  2. Biopsy shows white blood cell infiltration without blood vessel inflammation.

  Minor Criteria:

  1. Associated with an underlying condition like an infection, vaccination, inflammatory disease, cancer, or pregnancy.

  2. Fever above 38°C (100.4°F).

  3. Abnormal lab results, such as elevated ESR (inflammation marker), high C-reactive protein, increased white blood cells, or neutrophils.

  4. Excellent response to steroid treatment.

 

DRUG-INDUCED SWEET SYNDROME:

To diagnose this type, all five of the following criteria must be met:

1. Sudden onset of painful red bumps or lumps.

2. Biopsy showing white blood cells without blood vessel inflammation.

3. Fever above 38°C (100.4°F).

4. Symptoms starting after taking a certain drug, or after a drug challenge.

5. Lesions improve after stopping the drug or with steroid treatment.

 

DIFFERENTIAL DIAGNOSIS

• Allergic Contact Dermatitis: Typically shows a delayed hypersensitivity reaction with exposure to allergens.
• Cellulitis: A bacterial skin infection with redness, swelling, and warmth, often with systemic symptoms.
• Dermatologic Aspects of Behçet Disease: Features oral and genital ulcers, and skin lesions such as erythema nodosum or pseudofolliculitis.
• Dermatologic Manifestations of Herpes Simplex: Can present with vesicular lesions, commonly on lips or genitals.
• Drug Eruptions: Drug-induced skin reactions can vary widely but often include a history of recent medication use.
• Erythema Multiforme: Characterized by targetoid lesions and can be triggered by infections or medications.
• Erythema Nodosum: Presents with painful, erythematous nodules typically on the lower legs, often associated with systemic conditions.
• Pyoderma Gangrenosum: Presents with rapidly enlarging, painful ulcers, often with a neutrophilic infiltrate and can be associated with systemic disease.

These considerations and differential diagnoses are crucial for distinguishing Sweet syndrome from other conditions with similar presentations.

Laboratory Studies

1. Complete Blood Cell (CBC) Count with Differential:

• Purpose: Detects neutrophilia and screens for hematologic disorders or malignancy.
• Findings: Neutrophilia is typical; absence of neutrophilia in a neutropenic patient does not rule out Sweet syndrome. Anemia and thrombocytopenia may indicate underlying malignancy.
• Follow-Up: Abnormalities may warrant a bone marrow biopsy.

2. Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP):

• Purpose: Assess inflammation levels.
• Findings: Elevated ESR (>90% of cases) and CRP are common but nonspecific.

3. Urinalysis:

• Purpose: Identify renal involvement.
• Findings: May show proteinuria and/or hematuria.

4. Liver Functions Test:

• Purpose: Evaluate liver function.
• Findings: May show nonspecific elevation of hepatic enzymes.

5. Antineutrophilic Cytoplasmic Antibodies (ANCAs):

• Purpose: Investigate autoimmune components.
• Findings: Present in some patients but not consistent.

6. Cultures:

• Purpose: Rule out infections.
• Findings: Cultures should be obtained for bacteria, fungi, and mycobacteria.

 

Imaging Studies

1. Chest Radiograph:

·         Purpose: Evaluate for pulmonary involvement if symptoms are present.

·         Findings: Pulmonary symptoms are responsive to systemic corticosteroids.

2. Systemic Evaluation:

• Purpose: Investigate for underlying malignancy, especially if ulcerative lesions, oral lesions, or abnormal blood counts are present.
• Imaging: Use appropriate modalities for early detection and treatment of suspected malignancies.

 

3. FDG Positron-Emission Tomography (PET):

• Purpose: Assess myeloproliferative disorders and solid tumors.
• Findings: Useful for evaluating early malignancies.

Procedures

1. Skin Biopsy:

• Purpose: Confirm diagnosis.
• Findings: Dense neutrophilic infiltrate in the reticular dermis; massive papillary dermal edema. True vasculitic changes are absent.

2. Bone Marrow Aspiration:

• Purpose: Detect myelodysplastic disease.
• Indications: Abnormal CBC count or atypical bullous/ulcerative Sweet syndrome.

3. Cancer Screening and Evaluation for Inflammatory Bowel Disease:

• Purpose: Identify underlying causes, particularly in patients with bullous or ulcerative lesions.

 

Histologic Findings

• Classic Pattern: Dense neutrophilic infiltrate in the reticular dermis with massive papillary dermal edema. Leukocytoclastic nuclear debris may be present. True vasculitic changes are absent.
• Epidermis: Usually spared, but spongiosis and subcorneal pustules can be seen.
• Subcutaneous Involvement: Rare, but if present, shows extensive involvement of the reticular dermis.

Variants

1. Histiocytoid Sweet Syndrome:

·         Features: Includes histiocytoid cells, often mistaken for histiocytes.

·         Differential: Leukemia cutis.

2. Other Variants: Lymphocytic, subcutaneous, and cryptococcoid types.

 

Treatment & Management of Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome)

Sweet syndrome generally responds well to oral corticosteroids. Without treatment, the condition may persist for weeks to months, often resolving without leaving scars. However, recurrence is common in idiopathic and malignancy-associated forms. In some rare instances, lesions can recur or persist indefinitely. Malignancy-associated cases can also present with more severe, treatment-resistant bullous or ulcerative lesions, mimicking atypical pyoderma gangrenosum.

 

MEDICAL CARE

1. Corticosteroids:

·         Systemic Corticosteroids: Prednisone is the primary treatment, showing rapid effectiveness. The typical dosage is 0.5-1 mg/kg/day. For severe cases, 2 mg/kg/day divided into two doses may be required. Pulmonary infiltrates often respond promptly. Recurrence is common, and a slow tapering of the steroid is recommended to manage it.

·         Topical Corticosteroids: High-potency options like clobetasol propionate (0.05%) or intralesional glucocorticoids (e.g., triamcinolone acetonide 3-10 mg/mL) can be effective for localized lesions.

2. Steroid-Sparing Agents:

Indomethacin, Colchicine, Potassium Iodide: Useful in small series of patients. Colchicine, in particular, has been reported as effective in a retrospective study as a first-line therapy.

Dapsone, Cyclosporine, Etretinate, Pentoxifylline, Clofazimine: Have been used with anecdotal success.

Other Agents: Doxycycline, metronidazole, isotretinoin, methotrexate, cyclophosphamide, chlorambucil, adalimumab, infliximab, IVIG, pulse doses of methylprednisolone, and interferon-alfa have shown effectiveness in various cases.

3. Thalidomide: Used in recalcitrant cases when other treatments, including corticosteroids, metronidazole, dapsone, and methotrexate, fail.

4. Biologic Agents:

• Etanercept: Effective in some cases, particularly in rheumatoid arthritis patients. Caution is needed due to potential cancer risk.
• Anakinra and Rituximab: Reported as effective in refractory cases.
• Adalimumab: Effective in recalcitrant cases.

 

Consultations

• Dermatologist: For diagnosis, evaluation, and management of Sweet syndrome, as well as to identify underlying causes.
• Internal Medicine Specialist: For evaluation of underlying or triggering conditions.

This comprehensive approach helps in effectively managing Sweet syndrome, particularly by addressing both the disease itself and any underlying conditions or triggers.

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