Table I.
Categorization of clinical and histopathologic features of COVID-19 vaccine cutaneous reactions∗
| Clinical reaction pattern | Age (range), y | Vaccine brand (%) | Distribution | Morphology (based on clinical photograph review) | Histopathology | |
|---|---|---|---|---|---|---|
| V-REPP (n = 15) | ||||||
| Robust | Papulovesicular (n = 3) | 29-81 | Moderna (33%), Pfizer (67%) | Trunk, extremities > neck, face, head | Discrete edematous papules, some with central vesiculation and crusting | Spongiotic dermatitis as robust intercellular edema with intraepidermal vesicles, papillary dermal edema, and dermal eosinophils; interface changes may or may not be present |
| Moderate | Pityriasis rosea-like (n = 8) | 41-82 | Moderna (38%), Pfizer (50%), Oxford-AstraZeneca (12%) | Trunk, extremities > face | Oval, pityriasis rosea-like pink edematous papules and plaques, some with central crust and some with trailing scale | Spongiotic dermatitis >> interface changes and dermal eosinophils are often present |
| Mild | Papulosquamous with subtle scale (n = 4) | 31-71 | Moderna (50%), Pfizer (25%), Unspecified (25%) | Trunk, extremities | Oval or annular pink thin papules coalescing into plaques, with mild surface changes and subtle scale | Spongiosis as mild intercellular edema and vacuolar interface changes are present and may be focal; eosinophils may or may not be present |
| Bullous pemphigoid-like (n = 12) | ||||||
| 42-97 | Moderna (36%), Pfizer (64%) | Trunk, extremities > face, head, neck, oral mucosa, genital mucosa | Tense unilocular clear fluid-filled bullae on an erythematous base | Subepidermal blister formation and mixed inflammation with eosinophils
|
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| Dermal hypersensitivity reaction (n = 4) | ||||||
| 34-83 | Moderna (25%), Pfizer (25%), Unspecified (25%) | Trunk, extremities > face, neck | Pink edematous papules coalescing into plaques without surface change; individual lesions last >24 h | Perivascular infiltrate with mixed inflammation, which may include lymphocytes, neutrophils, and eosinophils | ||
| Herpes zoster (n = 4) | ||||||
| 39-78 | Moderna (50%), Pfizer (12%), Johnson and Johnson (25%) | Trunk, extremities, face | Grouped vesicles on an erythematous base not crossing the midline | All with viral cytopathic changes present. Involvement of the hair follicle in 2 of 4 cases | ||
| Lichen planus-like (n = 4) | ||||||
| 31-72 | Moderna (25%), Pfizer (75%) | Trunk, extremities | No clinical images | Lichenoid interface dermatitis; dermal eosinophils may be present | ||
| Pernio (n = 3) | ||||||
| 22-60 | Moderna (33%), Pfizer (67%) | Fingers, toes | Pink to violaceous papules of the toes? fingers too? Maybe just say toes > fingers or digits? | Perivascular lymphocytic infiltrate with papillary dermal edema and interface changes | ||
| Urticaria (n = 2) | ||||||
| 47-68 | Moderna (50%), Pfizer (50%) | Trunk, extremities, face | Erythematous, well-circumscribed papules and plaques without surface change lasting < 24 h | Dermal edema with sparse perivascular lymphocytes, neutrophils and eosinophils | ||
| Neutrophilic dermatosis (n = 2) | ||||||
| 68-93 | Moderna (50%), Pfizer (50%) | Trunk, extremities, face | Bright red to violaceous dermal papules and plaques | Dense dermal neutrophilic infiltrate with papillary dermal edema; leukocytoclasis and secondary vasculitic changes may be present | ||
| Leukocytoclastic vasculitis (n = 2) | ||||||
| 57-61 | Moderna (50%), Pfizer (50%) | Lower extremities | Deep red to maroon palpable purpura | Epidermal infiltrate of neutrophils and extravasated erythrocytes with perivascular neutrophils and leukocytoclasis | ||
| Morbilliform (n = 2) | ||||||
| 50-85 | Moderna (100%) | Trunk, extremities | No clinical images | Perivascular mixed infiltrate; interface changes may be present | ||
| Delayed large local reactions (n = 2) | ||||||
| 27-35 | Moderna (100%) | Vaccinated arm | Indurated, erythematous plaque | Superficial perivascular and perifollicular lymphocytic infiltrate with rare eosinophils and scattered mast cells | ||
| Erythromelalgia (n = 1) | ||||||
| 27 | Moderna (100%) | Hands, feet | Erythematous, edematous hands and feet (with burning sensation) | Superficial and deep perivascular inflammation and edema | ||
| Other (n = 5) | ||||||
| Stevens-Johnson Syndrome | 46 | Moderna (100%) | All skin surfaces, oral and genital mucosa | Atypical targetoid papules with duskiness, bullae, and epidermal necrosis in the center; hemorrhagic crusting on the vermillion lips; lesions involved palms and soles | Full-thickness epidermal necrosis | |
| Erythema multiforme | 42 | Moderna (100%) | Arms, hands | Erythematous, targetoid papules and plaques | Spongiotic and vacuolar interface dermatitis | |
| Granuloma annulare | 85 | Pfizer (100%) | Trunk | No clinical images | Interstitial granulomatous reaction | |
| Tattoo sarcoidal reaction | 38 | Moderna (100%) | Leg | No clinical images | Tattoo with suppurativa granulomatous inflammation | |
| New onset psoriasis | 67 | Moderna (100%) | Trunk, extremities, head, neck, face | Well demarcated erythematous papules and plaques with overlying silvery scale | Epidermal acanthosis, confluent parakeratosis with trapped clusters of neutrophils, and focal spongiform pustule formation. Diminished thickness of granular layer | |
BMZ, Basement membrane zone; BP, blood pressure; DIF, direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IgG, immunoglobulin G; V-Repp, vaccine-related eruptions of papules and plaques.
∗
These data from 58 biopsy reports represent a subset of the overall 803 cases in the registry, where biopsy was performed and the report was available for review. For clinical photos of these reactions see Supplemental Fig 1.