Is this biopsy finding consistent with Sweet syndrome or a side effect of Yervoy (ipilimumab)?

Biopsy Findings: Immune Checkpoint Inhibitor-Related Adverse Event, Not Sweet Syndrome

This biopsy is most consistent with an immune-related adverse event (irAE) from ipilimumab (Yervoy), not Sweet syndrome. The histopathologic features—focal epidermal erosion with minimal spongiosis, psoriasiform hyperplasia, and a superficial perivascular lymphohistiocytic infiltrate with eosinophils—align with the characteristic pattern of immune checkpoint inhibitor-induced dermatitis rather than the dense neutrophilic infiltrate required for Sweet syndrome diagnosis 1.

Key Distinguishing Histopathologic Features

The absence of dense neutrophilic infiltration in the dermis excludes Sweet syndrome. Sweet syndrome requires diffuse mature neutrophil infiltration localized predominantly to the upper dermis as a diagnostic criterion 2, 3, 4. Your biopsy instead shows:

• Lymphohistiocytic infiltrate with eosinophils (not neutrophils) 1
• Superficial perivascular pattern (not diffuse dermal infiltration) 1
• Sparing of deep dermis (Sweet syndrome typically involves upper dermis diffusely) 2

The presence of lymphocytic CD4+ infiltrates with eosinophils is specifically described as characteristic of immune checkpoint inhibitor-related maculopapular rashes and DRESS syndrome, not Sweet syndrome 1, 5.

Clinical Context Supporting ICI-Related Toxicity

Skin adverse events occur in 43-45% of patients treated with ipilimumab, typically developing within the first few weeks of treatment. 1 The histopathologic pattern you describe matches the documented findings in ipilimumab-related dermatitis:

• Psoriasiform hyperplasia is a recognized pattern in ICI-related skin toxicity, including psoriasiform reactions that can occur de novo without prior psoriasis history 1
• Eosinophils in the infiltrate are characteristic of ICI-related dermatitis and help distinguish it from other drug reactions 1, 5
• Minimal spongiosis with focal erosion fits the spectrum of ICI-related inflammatory skin changes 1

Why This Is Not Sweet Syndrome

Sweet syndrome has specific diagnostic requirements that are not met by this biopsy: 6, 2

1. Neutrophilic infiltrate is mandatory: Sweet syndrome requires dense, mature neutrophil infiltration diffusely distributed in the upper dermis 2, 3, 4
2. Clinical triad typically present: Sweet syndrome classically presents with tender erythematous papules/nodules/plaques, fever, and neutrophilia 6, 3
3. Different histologic pattern: Sweet syndrome shows neutrophilic infiltration without the lymphohistiocytic and eosinophilic pattern seen here 2, 4

While Sweet syndrome can rarely occur with ipilimumab (only a few case reports exist) 1, 7, the histopathology must demonstrate the characteristic neutrophilic infiltrate to make this diagnosis 6, 2.

Management Implications

This distinction is clinically important because management differs:

• For ICI-related dermatitis: Grade the severity by body surface area involvement, use topical corticosteroids for mild cases, and consider systemic corticosteroids (0.5-1 mg/kg prednisone) for grade 3 or higher reactions 1
• For Sweet syndrome: Would require systemic corticosteroids as first-line (considered "gold standard"), with potassium iodide or colchicine as alternatives 2, 3

The presence of eosinophils and lymphohistiocytic infiltrate suggests you should also consider DRESS syndrome in the differential, particularly if the patient has systemic symptoms, organ involvement, or eosinophilia 5, 8. DRESS typically occurs after 2-6 weeks of drug exposure and requires more aggressive immunosuppression than simple maculopapular rash 5, 8.

Recommended Next Steps

Correlate these histopathologic findings with clinical presentation: 1

• Assess body surface area involvement to grade severity
• Check for systemic symptoms (fever, organ involvement) that might suggest DRESS syndrome 5, 8
• Obtain complete blood count to evaluate for eosinophilia (>700/μL or >10%) and assess for neutrophilia versus lymphocytosis 8, 3
• Evaluate liver and kidney function if systemic involvement suspected 8

If clinical features suggest possible Sweet syndrome despite atypical histology, consider repeat biopsy of a different active lesion, as sampling error can occur 6. However, the current histopathology strongly favors ICI-related dermatitis over Sweet syndrome 1.