Reader Comment Regarding “Approach to Chilblains During the COVID-19 Pandemic”

Abstract

Dear Editor, The emergence of chilblains during the SARSCoV-2 pandemic has aroused great interest in the scientific community, given its clinical and epidemiological implications. The accumulated evidence suggests that chilblains may be a late COVID-19 manifestation with a favorable prognosis, affecting predominantly younger patients.1 Histopathologic findings include superficial and deep perivascular and perieccrine mononuclear infiltrate, and a variable degree of thrombosis in the dermal capillaries.2,3 Furthermore, some authors have been able to demonstrate the presence of SARSCoV-2 by PCR in skin biopsies.2 However, the underlying pathogenic mechanism behind this phenomenon remains uncertain. In this context, we have read with interest the article entitled “Approach to chilblains during the COVID-19 pandemic” recently reported by Ladha in the Journal.4 The authors propose an algorithm for the etiological diagnosis of chilblains in the COVID-19 era. This algorithm differentiates between primary COVID-19 chilblains and other causes, including idiopathic chilblains, cryoproteinemias, autoimmune conditions, and hematologic dyscrasias, among others. The authors rightly recognize that a negative nucleic acid test does not rule out COVID-19. However, they seem to have overlooked that several entities included in the differential may be, in turn, secondary to the SARSCoV-2 infection. In this regard, it should be noted that we have recently documented a high prevalence of cryofibrinogenemia (66.7%) in a series of 54 patients who presented with chilblains during the first pandemic peak in northern Spain.3 Although other cryoproteins have been previously studied in similar series, this is the first report of positive cryofibrinogen (CF) in patients with COVID-19 related chilblains. CF is an abnormal protein that may precipitate at low plasma temperatures, causing thrombotic occlusions of small to medium arteries. The presence of CF may, in turn, be primary or secondary to an underlying disorder, including collagen diseases, vasculitis, malignant diseases, and infections. In the context of an infection, CF may precipitate due to its interaction with circulating immunoglobulins, immune complexes, and fibronectin.5 In this sense, CF may appear as a SARSCoV-2 infection epiphenomenon that could explain the clinical and histopathological findings in COVID-19related chilblains.3 CF deposits in secondary cryofibrinogenemia progressively dissolve when the underlying cause is treated, but moderate to severe cases may require additional treatment with platelet antiaggregants, corticosteroids, immunosuppressants, and fibrinolytic agents.5 It is noteworthy that most of the other cutaneous manifestations observed in patients with COVID-19, including purpura, livedo reticularis, urticaria, blisters, and necrotic ulcerations,1 have been previously described in patients with cryofibrinogenemia.5 However, the presence of CF in COVID-19 patients with cutaneous manifestations other than chilblains has not been investigated to date. Moreover, knowing that cryofibrinogenemia may cause thrombotic events at different levels and given the potential clinical and therapeutic implications, we believe that patients with COVID-19 and prothrombotic activity should also be investigated for CF. In conclusion, we suggest that the algorithm proposed by Ladha et al. should be revised since SARSCoV-2 infection and some of the alternative etiologic diagnoses proposed, particularly cryofibrinogenemia, may not be mutually exclusive conditions.