University of Pennsylvania

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

Erythromelalgia associated with dermatomyositis: A case series.

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Registry analysis does not measure incidence. Morphologic misclassification is possible. We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons.

Inherited erythromelalgia/erythermalgia (IEM) is a neuropathy characterized by pain and redness of the extremities that is triggered by warmth. IEM has been associated with missense mutations of the voltage-gated sodium channel Na(V)1.7, which is preferentially expressed in most nociceptive dorsal root ganglia (DRGs) and sympathetic ganglion neurons. Several mutations occur in cytoplasmic linkers of Na(V)1.7, with only two mutations in segment 4 (S4) and S6 of domain I. We report here a simplex case with an alanine 863 substitution by proline (A863P) in S5 of domain II of Na(V)1.7. The functional effect of A863P was investigated by voltage-clamp analysis in human embryonic kidney 293 cells and by current-clamp analysis to determine the effects of A863P on firing properties of small DRG neurons. Activation of mutant channels was shifted by -8 mV, whereas steady-state fast inactivation was shifted by +10 mV, compared with wild-type (WT) channels. There was a marked decrease in the rate of deactivation of mutant channels, and currents elicited by slow ramp depolarizations were 12 times larger than for WT. These results suggested that A863P could render DRG neurons hyperexcitable. We tested this hypothesis by studying properties of rat DRG neurons transfected with either A863P or WT channels. A863P depolarized resting potential of DRG neurons by +6 mV compared with WT channels, reduced the threshold for triggering single action potentials to 63% of that for WT channels, and increased firing frequency of neurons when stimulated with suprathreshold stimuli. Thus, A863P mutant channels produce hyperexcitability in DRG neurons, which contributes to the pathophysiology of IEM.

Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment.

Erythromelalgia is a rare, chronic, debilitating condition characterized by redness, warmth, and severe burning pain of the distal extremities. The feet are more commonly affected than the hands. Pain is precipitated by increases in temperature and by exercise. Patients often obtain relief by immersing the affected extremity in cold water. The pain is often refractory to treatment. For many patients, multiple pain medications have been useless in achieving complete relief of pain symptoms. Previous reports of erythromelalgia among adolescents indicated prolonged relief of pain with sodium nitroprusside infusions, epidural infusions of local anesthetics, or gabapentin treatment. We present a case of an 11-year-old, white, male child with primary erythromelalgia, whose initial symptoms started in his preschool years and whose childhood was marked by escalating episodes of pain with warmth and redness of his feet, precipitated especially by increases in temperature and by activity. All conventional pain management techniques had failed to relieve our patient of his symptoms, and he obtained some relief only by soaking his affected extremities in ice water. He had experienced minimal benefit from seeing a pain psychologist, who helped him develop techniques to cope with the pain. At the time of presentation, the patient's episodes of pain had increased to 15 to 20 per day, and there was evidence of chronic immersion injury to the skin of his feet. Before his most recent hospitalization, the pain had spread to involve his hands as well. The patient was overwhelmed with anxiety and could not participate in school or social activities at the time of admission. During his current hospitalization, he did show some therapeutic response to sodium nitroprusside infusion, which unfortunately had to be discontinued because of side effects and because his family desired to leave the ICU environment, which was stressful to the patient. He also had some response to lumbar epidural infusion of local anesthetics, which could not be continued because he found the motor blockade that accompanied his analgesia intolerable. However, intravenous lidocaine infusion, with subsequent transition to oral mexiletine therapy, proved very effective in reducing the frequency and severity of the pain episodes. The patient was discharged from the hospital with oral mexiletine therapy and has been monitored at the pain management clinic. He returned to and completed school, attended summer camp, and enjoys an active happy life. He walks without precipitating pain in his feet and sleeps 9 to 10 hours every night. He has needed to soak his feet on only 4 occasions in the 6 months since his discharge from the hospital. His quality of life has improved significantly. He has shown no evidence of liver toxicity, and his mexiletine levels have been stable.