Which neutrophilic dermatoses can cause chronic discharging sinus tracts in a patient with acute promyelocytic leukaemia who has completed induction or consolidation therapy and is currently or recently receiving all‑trans retinoic acid, and how should they be diagnosed and managed?

Neutrophilic Dermatoses Post-APML Treatment with ATRA

Primary Diagnosis: Sweet's Syndrome (Acute Febrile Neutrophilic Dermatosis)

Sweet's syndrome is the neutrophilic dermatosis that presents as chronic discharging sinus tracts or painful erythematous nodules in APML patients receiving ATRA, and it requires immediate recognition to differentiate from infection and prompt corticosteroid therapy. 1, 2, 3, 4

Clinical Presentation

Sweet's syndrome in ATRA-treated APML patients typically manifests as:

• Painful erythematous cutaneous plaques or nodules on the extremities, trunk, axillary areas, lower abdomen, and inguinal regions 1, 2, 3
• Fever accompanying the skin lesions, creating diagnostic confusion with infectious processes 2, 4
• Progression to subcutaneous nodules that may evolve into blisters with purple, necrotic bases that can discharge 4
• Bilateral distribution is common, particularly affecting axillary and inguinal areas 1

The timing is critical: these lesions typically develop during active ATRA therapy, most commonly during induction or consolidation phases 1, 2, 3, 4

Diagnostic Approach

Immediate Steps

Perform skin biopsy of the most representative lesion to establish diagnosis before initiating empiric therapy 1, 2, 3, 4

The pathognomonic histologic findings include:

• Dense dermal infiltrate of mature neutrophils without vasculitis 1, 2, 3
• Absence of cutaneous immunoglobulin deposits to exclude vasculitis 2
• No evidence of infectious organisms on special stains 1, 2

Critical Differential Diagnosis

The major diagnostic challenge is distinguishing Sweet's syndrome from:

• Infectious cellulitis or abscess - particularly problematic given concurrent fever and neutropenia risk 2, 4
• ATRA differentiation syndrome - which can coexist with Sweet's syndrome and presents with fever, respiratory distress, and pleural effusions 4
• Drug eruption - less likely given the specific neutrophilic infiltrate pattern 3

A key pitfall: physicians often misdiagnose Sweet's syndrome as infection and delay appropriate corticosteroid therapy while pursuing prolonged antibiotic trials. 2, 4

Management Algorithm

Step 1: Immediate Assessment

• Do not discontinue ATRA immediately unless differentiation syndrome is suspected 3, 4
• Obtain skin biopsy urgently (within 24 hours) 1, 2
• Assess for differentiation syndrome criteria: respiratory distress, weight gain >5kg, pleural/pericardial effusions, hypotension 4

Step 2: Initiate Corticosteroid Therapy

High-dose methylprednisolone (1-2 mg/kg/day IV) is first-line therapy and produces dramatic improvement within 24-48 hours 1, 2

Alternative regimen:

• Oral prednisone 0.5-1 mg/kg/day for less severe cases 2
• Expect clinical response within 24-48 hours - lack of response should prompt reconsideration of diagnosis 1, 2

Step 3: ATRA Management Decision

Continue ATRA if Sweet's syndrome is isolated (no differentiation syndrome features) and patient responds to corticosteroids 3

Suspend ATRA if:

• Differentiation syndrome is present (fever, respiratory distress, hypotension, effusions) 4
• Sweet's syndrome progresses despite adequate corticosteroid therapy 4
• Patient develops shock or multi-organ dysfunction 4

The evidence shows that low-dose corticosteroids (as used for differentiation syndrome prophylaxis at 0.5 mg/kg/day) are insufficient for treating established Sweet's syndrome 3

Step 4: Duration of Therapy

• Continue corticosteroids until complete resolution of skin lesions (typically 2-4 weeks) 1, 2
• Taper gradually to prevent rebound 2
• Resume or continue ATRA once Sweet's syndrome is controlled if differentiation syndrome was not present 3

Relationship to Differentiation Syndrome

Sweet's syndrome can occur as part of differentiation syndrome or independently 4

When Sweet's syndrome complicates differentiation syndrome:

• Prophylactic dexamethasone 0.5 mg/kg/day (as recommended by ESMO guidelines for all ATRA-treated patients) may not prevent Sweet's syndrome 5, 4
• Higher corticosteroid doses are required for treatment than for prophylaxis 3, 4
• ATRA suspension is mandatory until clinical stabilization 4

Prognosis and Outcomes

Sweet's syndrome responds dramatically to corticosteroids with resolution within 24-48 hours, and does not compromise the excellent long-term outcomes of APML when managed appropriately 1, 2, 3

The critical mortality risk remains hemorrhage from coagulopathy during induction, not dermatologic complications 5, 6

Key Clinical Pearls

• Sweet's syndrome is rare but well-documented in ATRA-treated APML patients across all age groups, including children 1, 2, 3, 4
• Fever with skin lesions during ATRA therapy should not automatically trigger ATRA discontinuation - obtain biopsy first 2, 3
• The presence of mature neutrophils on histology distinguishes this from leukemia cutis (which shows immature blasts) 1, 2
• Discharging sinuses represent advanced Sweet's syndrome with necrosis and require aggressive corticosteroid therapy 4