Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome)

Introduction:

• Definition: A rare skin condition with fever and inflamed or blistered skin and mucosal lesions.
• Type: Autoinflammatory disorder often linked to systemic diseases.
• Eponym: Also known as Sweet syndrome, named after Dr. Robert Douglas Sweet who described it in 1964.

Demographics:

• Commonly Affected: Mostly middle-aged women, but also men, children (rarely), and the elderly.
• Genetic Marker: More frequent in individuals with HLA-B54.
• Health Context: Can occur in healthy individuals or alongside acute systemic infections or chronic conditions.

Etiology of Sweet Syndrome

• Primary Types:
  • Idiopathic: Most common form.
  • Associated with Underlying Conditions: Malignancies, inflammatory diseases, infections, and drug reactions.

Malignancy-Associated Sweet Syndrome:

• Correlated Malignancies:
  • Myeloproliferative disorders: Myelodysplasia, acute myelogenous leukemia, chronic myelogenous leukemia.
  • Multiple myeloma, monoclonal gammopathy.
  • Lymphoma, and occasionally solid tumors.
• Timing: May occur before, during, or after the diagnosis of malignancy.
• Characteristics: More common with older age of onset and cytopenias.
• Histiocytoid Sweet Syndrome: Stronger link with malignancies, especially myelodysplastic syndrome.

Inflammatory and Autoimmune Disease Associations:

• Conditions: Inflammatory bowel disease (ulcerative colitis, Crohn’s disease), rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, Hashimoto thyroiditis, Behcet disease, dermatomyositis.

Post-Infectious Sweet Syndrome:

• Onset: Occurs 1 to 3 weeks after upper respiratory or gastrointestinal infections.
• Infections: HIV, viral hepatitis, tuberculosis, and occasionally chlamydia.

Drug-Induced Sweet Syndrome:

• Common Trigger: Granulocyte-colony stimulating factor (G-CSF).
• Other Medications:
  • Antibiotics: Minocycline, nitrofurantoin, trimethoprim-sulfamethoxazole, norfloxacin, ofloxacin.
  • Antihypertensives: Hydralazine, furosemide.
  • NSAIDs: Diclofenac, celecoxib.
  • Immunosuppressives: Azathioprine.
  • Antiepileptics: Carbamazepine, diazepam.
  • Anti-cancer: Bortezomib, imatinib mesylate, ipilimumab, lenalidomide, topotecan, vemurafenib.
  • Antipsychotics: Clozapine.
  • Antithyroid: Propylthiouracil.
• Reaction Pattern: Occurs after initial exposure and may recur with re-exposure, resolving after drug withdrawal, sometimes with corticosteroids.

Pregnancy-Related Sweet Syndrome:

• Prevalence: Occurs in about 2% of cases.
• Prognosis: Typically resolves spontaneously after delivery, with no significant maternal or infant morbidity or mortality.

Triggers:

• Idiopathic Cases: Many cases have no identifiable underlying condition.
• Sun exposure
• Upper respiratory infections
• Inflammatory bowel diseases
• Autoimmune diseases (e.g., rheumatoid arthritis, lupus)
• Blood disorders (e.g., leukemia, myelodysplastic syndromes)
• Internal cancers
• Pregnancy
• Gastrointestinal infections
• Vaccinations
• Certain medications
• Immunodeficiency

Symptoms:

• General: Can be a single occurrence or recurrent.
• Common Symptoms:
  • Fever (high or moderate)
  • Fatigue and malaise
  • Skin lesions
  • Sore eyes or mouth ulcers
  • Joint pain
  • Headache
  • Other organ involvement (e.g., bones, nervous system, kidneys, intestines, liver, heart, lungs, muscles, spleen).

Appearance of Skin Lesions:

• Characteristics: Tender, possibly very painful, lasting days to weeks.
• Common Sites: Limbs and neck, possibly sun-exposed areas.
  • Rare Locations: Oral and genital lesions, with oral ulcers especially linked to hematological malignancies.
• Types of Lesions:
  • Small papules or vesicles
  • Larger plaques or nodules
  • Pseudovesicular appearance
  • Annular lesions
  • Erosions and ulcers resembling atypical pyoderma gangrenosum.

Constitutional Symptoms:

• Fever: Typically present, particularly in drug-induced cases, though absent in 10-20% of cases linked to other causes.
• Other Symptoms: Arthralgia, myalgia, fatigue, malaise, and headache.

Extracutaneous Manifestations:

• Joint Involvement:
  • Prevalence: Occurs in 30-60% of cases.
  • Types: Arthralgias and non-erosive inflammatory arthritis.
• Ocular Inflammation:
  • Common: Conjunctivitis.
  • Other Manifestations: Episcleritis, scleritis, keratitis (including peripheral ulcerative keratitis), uveitis, and choroiditis.
• Systemic Involvement: Rare cases include:
  • Myocarditis
  • Multifocal Sterile Osteomyelitis
  • Alveolitis
  • Pleural Effusions
  • Aseptic Meningitis

Diagnosis:

• Clinical: Often based on symptoms and skin biopsy.
• Criteria:
  • Major: Abrupt onset of tender or painful red/purplish plaques/nodules, biopsy showing neutrophil-dominant inflammation without vasculitis.
  • Minor: Preceding fever/infection, systemic symptoms, raised white cell count, response to systemic steroids, elevated ESR.

Blood Tests:

• Findings: Raised ESR/CRP, neutrophil leukocytosis, possible presence of ANCA.
• Serious Conditions: Full blood count may indicate serious underlying blood disorders.

Treatment:

• First-Line: Systemic steroids (e.g., predniso(lo)ne 30-60 mg daily).
• Alternative Medications:
  • Topical/intralesional corticosteroids
  • Colchicine
  • Potassium iodide solution
  • Dapsone
  • NSAIDs
  • Immunosuppressants (e.g., ciclosporin, anakinra)
  • Antibiotics (e.g., minocycline)
  • Other agents (e.g., thalidomide, biologics like infliximab).

Outcome:

• Resolution: Typically resolves without scarring, though subcutaneous forms can leave skin indentations.
• Recurrence: Possible in a third of patients, especially those with underlying myelodysplasia or cancer.
• Persistent Cases: Severe cases associated with malignancy may persist despite treatment