Cutaneous Rosai-Dorfman disease after Covid 19 vaccination treated with thalidomide.

We report here, to the best of our knowledge, the first case of cutaneous Rosai-Dorfman disease observed following vaccination against coronavirus-19 disease. Reports of COVID-19 vaccine-related skin reactions have become frequent. The most common reports concern injection site reactions and maculo-papular or urticarial rashes. However, many different skin manifestations have been observed.1 An otherwise healthy, 62-year-old individual came to our Dermatology Outpatient Clinic for a generalized, itchy, papular eruption, which had lasted for 6 months. He reported no other systemic symptoms, and in his medical history nothing relevant emerged. He received his first dose of Pfizer® vaccination against COVID-19 in June 2021. After 10 days, he noticed the appearance of small, itchy, purplish papules on his legs; a few days after the second dose, these lesions spread gradually on the trunk and upper limbs. On clinical examination we observed purpuric papules symmetrically distributed on the upper and lower limbs, trunk, and neck (Figure 1A–C). Some of these lesions were keratotic. The patient had no enlarged lymphnodes. Histopathological examination showed large histiocyte-rich dermal infiltrate S100+ with emperipolesis, surrounded by lymphocytes, plasma cells, and neutrophils (Figure 1D,E). No BRAF or KRAS mutations were found. These findings were characteristic of a rare non-Langerhans cell histiocytosis of Rosai-Dorfman-Destombes type (RDD). Laboratory tests showed only a mild anemia 12.5 g/dl (normal range 14.0–17.0). As no internal abnormalities were recognized on the computed tomography scan and on the lymph nodes and abdominal ultrasound, we opted for the diagnosis of cutaneous Rosai-Dorfman disease (cRDD). Based on several reports on its safety-to-efficacy balance, we prescribed oral thalidomide2 100 mg/day and, after 6 months, we observed that lesions had cleared with no adverse effects. To date, no cases of cutaneous histiocytosis have been reported after Covid-19 vaccination, while one case of cRDD has been described after Pneumococcal vaccination.1, 3 Primary cRDD is a form of non-Langerhans cells histiocytosis limited to the skin and mucosal surfaces (“group C histiocytoses”) in 3% of the cases. It may be indolent with a self-limiting course, but follow-up is indispensable, as systemic involvement cannot be excluded. Lesions are typically slow-growing, painless papules, nodules or plaques with color ranging from red to brown.4 Etiopathogenesis is unknown but it may be secondary to a malignant, infectious (i.e., Epstein–Barr Virus, Cytomegalovirus, and parvovirus B19), or autoimmune/autoinflammatory stimulus.5 The frequent presence of monoclonality of histiocytes raises the question whether it should be considered a neoplasm. The histological marker is the presence of large, pale histiocytes with emperipolesis, while immunochemistry shows positivity for S100 protein and for histiocytic markers—CD68 and CD163—and OCT2, but negativity for Langerhans cell markers—CD1a and CD207.6 In most cases, mutations of BRAF, KRAS, and NRAS are detected. For the treatment of refractory or extensive disease, there is some evidence of effectiveness for thalidomide, dapsone and low-dose weekly methotrexate as monotherapy, or combined with steroids.7 Histiocytes perform phagocytic functions against numerous antigens, so different stimuli can trigger their activation and proliferation. However, the precise mechanism that determines the appearance of these lesions after vaccination against Covid-19 has not yet been clarified. Another condition that links histiocytes to COVID-19 is a macrophage hyperactivation syndrome called Hemophagocytic lymphohistiocytosis (HLH), found both post-COVID-19 infection and post-vaccination. This could be due to an altered response of macrophages against virus-infected cells with modification of their cytotoxic function.8 We report this association for the first time, given that the strict temporal relationship between vaccination and development of this dermatosis may be of a causal nature.9 Marta Grimaldi, Biagio Didona, and Luca Fania visited the patient, Francesca Ricci performed histological examination; all authors discussed the case report, wrote the manuscript and contributed to the final manuscript. This study was in part supported by the “Progetto Ricerca Corrente – RC4.3 2021-2022” of the Italian Ministry of Health, Rome, Italy. The authors declare no potential conflict of interest. The patient described in this manuscript has given written informed consent to the publication of their case details. Data sharing is not applicable to this article as no new data were created or analyzed in this study.