Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2025;15(1):4929 1 Reflectance Confocal Microscopy of Sweet Syndrome François Skowron1, Amélie Carbonnelle-Puscian2, Marco Ardigò3 1 Department of Dermatology, Hôpitaux Drôme Nord, Romans-Sur-Isère, France 2 Dermapath Network, Cypath, Villeurbanne, France 3 Department of Biomedical Sciences, Humanitas University, Milan, Italy Key words: Confocal Microscopy, Neutrophilic Dermatosis, Biopsy, Diagnosis Citation: Skowron F, Carbonnelle-Puscian A, Ardigò M. Reflectance Confocal Microscopy of Sweet Syndrome. Dermatol Pract Concept. 2025;15(1):4929. DOI: https://doi.org/10.5826/dpc.1501a4929 Accepted: August 26, 2024; Published: January 2025 Copyright: ©2024 Skowron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: François Skowron- Department of Dermatology, Hôpitaux Drôme Nord, 607 avenue Geneviève De Gaulle- Anthonioz, 26102 Romans-Sur-Isère, France Introduction Sweet syndrome or acute febrile neutrophilic dermatosis is a rare disease, characterized by an acute onset of tender er- ythematous plaques with dense neutrophilic infiltrate in the dermis [1]. Case Presentation A 57-year-old woman developed multiple sore papules ini- tially on the shoulders that within 3 days extended to the trunk, upper limbs, and thighs along with a mild fever 38°C. Her medical history revealed penicillin hypersensitivity and functional colonic disease. Papules were erythematous, edematous, enlarged up to 3 cm, and had a central darker area. Blood count, ionogram, C-reactive protein and renal function were normal. A papular lesion on the wrist was analyzed (Figure 1A). Dermoscopy showed homogenous vi- olaceous pattern with some pinpoint reinforcements and a central purpuric zone (Figure 1B). Reflectance confocal mi- croscopy (RCM) showed dark areas and numerous, single or aggregates, bright cellular structures of different shapes at the dermo-epidermal junction (Figure 2A) and some isolated bright cells surrounded by a dark acellular area at upper epidermal layers (Figure 2B). Biopsy revealed an acanthotic epidermis, intense papillary edema, and an intense poly- morphous inflammatory infiltrate in the dermis composed mainly of neutrophils. There was no leukocytoclasia or vas- culitis (Figure 1C). An idiopathic Sweet syndrome was diag- nosed. The eruption resolved over 3 weeks with a regimen of systemic corticosteroid with progressive tapering. A work-up revealed no sepsis, no cancer, no hemopathy, or inflamma- tory diseases. Conclusions Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare disease affecting typically women in the third through 2 Research Letter | Dermatol Pract Concept. 2025;15(1):4929 Figure 2. RCM findings: (A) Dark areas and numerous, single or aggregates, bright cells of different shape resembling polymorpho-nucleated cells (green arrow) at dermo-epidermal junction and (B) some isolated bright cells surrounded by a dark acellular area at upper epidermal layers. Figure 1. Clinical findings: (A) Multiple erythematous papules with central darker area on the upper trunk and arms (green marker 01: recent papular lesion on the wrist analyzed). (B) Dermoscopy: homogenous violaceous pattern with some pinpoint reinforcements and a central purpuric zone. (C) Histological findings (H&E, original magnification ×10): intense papillary edema, and an intense polymorphous inflammatory infiltrate in the dermis composed mainly of neutrophils. sixth decades [1]. The patient presents with a rapid onset of tender, sharply demarcated inflammatory papules on the face, upper chest and back, which spread over the trunk and limbs in a few days. Most cases are idiopathic, and some- times they are associated with drug reaction, infection, cancer, or inflammatory diseases. Dense neutrophilic infil- trate in the dermis without leukocytoclastic vasculitis is a major criterion for definite diagnosis of Sweet syndrome [2]. Intense papillary edema is another frequent histologic feature. Reflectance confocal microscopy (RCM) is a Research Letter | Dermatol Pract Concept. 2025;15(1):4929 3 noninvasive diagnostic tool that evaluates the epidermis and papillary dermis at a cellular level. It has been shown that RCM is efficient in psoriasis in monitoring neutrophils which appear as bright round to oval cells surrounded by a dark acellular area [3]. Edema appears as dark homogenous area just below the epidermis [4]. In our case report, RCM allowed us to observe these 2 important histologic criteria: intense neutrophilic infiltrate and papillary edema. One limit of RCM is the inability to determine presence or absence of vasculitis. However, it seems that RCM findings with neu- trophilic infiltrate and dermal edema, in a context of abrupt tender erythematous lesions on the upper trunk and limbs, is helpful in diagnosing Sweet syndrome and swiftly initiating corticosteroid systemic treatment. 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