key: cord-0713199-dy5me6bk authors: Kha, Connie; Itkin, Aleksandr title: New-onset chilblains in close temporal association to mRNA-1273 (Moderna) vaccination date: 2021-04-03 journal: JAAD Case Rep DOI: 10.1016/j.jdcr.2021.03.046 sha: 5f9e3f30fd9ef2f34448895b5c87713114c4bfea doc_id: 713199 cord_uid: dy5me6bk nan Chilblains are one of the Q4 earliest and most commonly described cutaneous manifestations of COVID-19; 1 however, more recent data have failed to suggest an association. As widespread vaccinations are underway, reports of delayed-type hypersensitivity reactions in recipients of the mRNA-1273 vaccine have been brought to attention. Here, we present a case of biopsy-confirmed chilblains developing shortly after vaccination in an asymptomatic healthcare worker, who was not tested for SARS-CoV-2. A 70-year-old woman presented to our Southern California dermatology clinic with an acute-onset of a pruritic papular rash on the digits of her right hand, Q5 which appeared 2 days after she had received her first dose of the mRNA-1273 vaccine. Of note, she was an asymptomatic healthcare worker with no history of COVID-19, and she had never been tested for the disease. A few scattered red edematous papules on an erythematous/violaceous background were noted on the palmar and lateral aspects of the fingers on her right hand (Fig 1) . The left hand was unaffected. Associated symptoms included erythema, swelling, and pain with movement of the right proximal interphalangeal joints of the 4th and 5th digits. These joint symptoms resolved within 10 days without treatment; however, the rash persisted. Her medical history was notable for pityriasis lichenoides chronica (PLC), which remained clinically stable with as-needed clobetasol 0.05% ointment. She denied recent exposure to cold or damp environments. A complete physical examination was unremarkable except for a few lesions consistent with PLC located on the extensor surfaces of the extremities. A complete blood count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Sj€ ogren antibodies (anti-SS-A/anti-SS-B), and antinuclear antibody were either within normal limits or negative. A 3-mm punch biopsy was obtained from the edge of a red papule located on the ulnar side of the 4 th distal phalanx on the right hand (Fig 1, C ) . Histopathology revealed a dense and predominantly perivascular lymphocytic infiltrate within the superficial-to-deep reticular dermis (Fig 2, ). The epidermis appeared normal with no vacuolar changes at the epidermal-dermal junction. There was a notable papillary dermal edema. Within the superficial dermis, some vessels exhibited slightly thickened walls with trophism of lymphocytes, although vascular wall hyalinization, neutrocytosis, or intravascular thrombi were not evident (Fig 2, B) . Immunohistochemical analysis demonstrated a majority of CD3 1 T cells in the lymphocytic infiltrate. Immunohistochemical results were otherwise negative. A diagnosis of chilblains was established based on histologic findings. The patient was treated with clobetasol 0.05% ointment applied twice daily. At the 2-week followup visit, complete resolution of the rash was observed. A similar rash occurred on the same hand 3 days after she received her second dose of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 the vaccine, which resolved in one week with topical steroid therapy. The injection site was on the left arm in both instances. Due to conflicting evidence, a causal relationship between SARS-CoV-2 infection and chilblains has not been established. Since the beginning of the COVID-19 pandemic, chilblain-like lesions have been observed in adults with severe disease and in asymptomatic or mildly symptomatic younger patients. 2, 3 The hypothesis of a robust antiviral type I interferon response in younger patients leading to early viremia clearance has been inconclusive, since few patients were tested for SARS-CoV-2 by reversetranscriptase polymerase chain reaction and serology in the early reports. [1] [2] [3] Now with greater availability of resources, researchers are testing larger sample sizes and at different stages of the disease. Recent series have demonstrated a statistically significant number of patients with chilblains who have tested negative for SARS-CoV-2 by reversetranscriptase polymerase chain reaction and serology, thereby not suggesting any causal relationship between chilblains and COVID-19. [4] [5] [6] In a smaller study, SARS-CoV-2 PCR swabs were negative 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 in 6 out of 7 pediatric patients with biopsy-confirmed chilblains. However, immunohistochemical staining was positive for SARS-CoV-2 spike protein in endothelial cells in all patients. 7 Interferonopathies, such as classic chilblains and associated variants, are characterized by an abnormal inflammatory and vascular response. Pardi et al 8 illustrated the potential of mRNA vaccines to induce potent type I interferon reactions, which are well known to stimulate cytokine-mediated autoinflammatory responses. Interestingly, we observed the development of chilblains shortly after vaccination in an older adult patient, in which such robust immune responses are uncommonly seen. Chilblains are typically seen following exposure to cold, damp environments, while less commonly seen in warmer climates, such as Southern California; however, chilblains may present during the winter season even in this region. There are 2 cases of chilblains in Southern California reported in the literature, 9 and our clinic has seen an increase of chilblains during these past winter months. Our patient was vaccinated during these colder months, which obscures the relationship between her cutaneous eruption and the vaccine. It should be noted that our patient has a history of PLC, which has been described to affect acral surfaces, 10 and which can present with lesions resembling those in Fig 1. However, a diagnosis of PLC was ruled out based on histological examination featuring typical characteristics of chilblains. Our case presentation does not prove a causal relationship between the mRNA-1273 vaccine and the development of chilblains. However, the temporal relationship between the rash onset and the date of vaccination and the development of the rash with each subsequent dose are in support of our observation Q7 . Several vaccine surveillance systems are in place to collect safety and adverse reactions data, which can provide further insight, as widespread vaccination continues. Until then, the purpose of this report is to alert clinicians of the possible side effect of the mRNA-1273-induced chilblains and to reassure patients that obtaining the second dose of the vaccine is safe and should not be delayed. 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients Going viral: a brief history of Chilblain-like skin lesions Chilblains and COVID-19: further evidence against a causal association Evaluation of chilblains as a manifestation of the COVID-19 pandemic Assessment of acute acral lesions in a case series of children and adolescents during the COVID-19 pandemic SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases mRNA vaccines -a new era in vaccinology Chilblains in Southern California: two case reports and a review of the literature Localized acral pityriasis lichenoides chronica: report of a case None declared.