The acral pseudochilblain pattern of lesions, reported by Galván et al.11 as acral, erythematous, and edematous lesions, with formation of vesicles and pustules, are perhaps the most characteristic skin lesions associated with the SARS-CoV-2 pandemic. The description and reporting of these lesions initially occurred outside academic circles in an informal fashion in medical or dermatological social media, based on shared images from family members, acquaintances, and colleagues. The first case published reported an adolescent aged 13 years who developed purpuric lesions on the feet prior to developing systemic symptoms such as fever, muscle pain, and headache, in a family with suspected cases of COVID-19 infection at the time the pandemic in Italy was spreading rapidly.12 However, no specific microbiological studies were performed. In the article, the authors mentioned the existence of an epidemic of similar lesions in children with suspected COVID-19 in Italy. In the series by Galván et al.,11 the pattern of pseudochilblain lesions was the second most common skin manifestation (19%). They developed in young patients, generally late on in the course of the disease, and were present for a period of 12.7 days, in general, in patients with mild disease or asymptomatic individuals. These lesions were described as painful (32%) or itchy (30%).

From the clinical point of view, the pseudochilblain pattern of lesions consists of macules, papules, or plaques, often about a millimeter in size, and usually with a clearly defined border in the metatarsophalangeal area, although the whole of the finger or toe can be involved (Fig. 1). Often, only some fingers or toes are affected while others completely lack any involvement, and at times, these lesions may be accompanied by lesions in the palmar and plantar region. They usually affect the feet and, to a lesser degree, the hands. Initially purpuric or bluish, they can form blisters or scabs during the course of the disease; at times, they may resemble multiform erythema13 or vasculitis; in fact, some authors recognize a multiform erythema type subgroup,13–15 with targetoid or atypical target lesions, which can be associated with lesions in extensor areas, such as the elbows. In cases with histological study, a lymphocytic infiltrate is reported in the superficial and deep dermis, of perivascular predominance, occasionally associated with edema and signs of endothelial activation.14 Keratinocyte necrosis and perieccrine reinforcement may be present.15

Figure 1.

Acral pseudochilblain papule.

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Alramthan and Aldaraji,16 reporting 2 clinical cases in young adults, proposed the hypothesis, not confirmed with histology in their own cases, that formation of hyaline thrombi in small caliber vessels of different organs observed in autopsies of patients could explain the pseudochilblain characteristics of the lesions.

Fewer than half the cases had microbiological or serological test results available (specific PCR or rapid antibody test for IgM/IgG). In general, when assessed, laboratory abnormalities or elevations have generally been lacking in measures of inflammation such as D-dimer, C reactive protein (CRP), or lactate dehydrogenase (LDH), indicative of poor prognosis for this disease. The strongest evidence of association with viral infection was therefore that presentation occurred during the pandemic (and in a different context to that of chilblains, in the warmer months than when they usually appear) and a history in the family environment or personal situation consistent with infection. The authors suggested these negative results were due to the late development of these lesions in the course of the disease; the low sensitivity of the tests used, which has led to mass recall of some batches; and the rapid disappearance of antibodies.11,15

Docampo-Simón et al.,17 in the first prospective study of skin manifestations, found a positive PCR result in only 1 of the 38 samples tested. In addition, due to the aforementioned technical reasons (time since infection, false negatives), the authors considered the possibility that this manifestation simply has nothing to do with COVID-19. Other possible explanations could be a traumatic origin during lock-down or even the concurrent expansion of another virus, such as parvovirus B19. This possible relation with the lock-down period, and not necessarily with COVID-19, has also been suggested in a recent series with similar results.18

During the worst weeks of the pandemic, we saw patients with these characteristics almost on a daily basis in our clinics. From both the clinical and epidemiological point of view, the characteristics are consistent with those described above. Most of our patients were young, asymptomatic or with mild symptoms, and not one of them had a serious complication associated with COVID-19.

In 8 Italian centers, clinical data were collected from patients with COVID-19, with microbiological confirmation by RT-PCR from a nasopharyngeal swab and with no history of medications that could have triggered chickenpox-like lesions. In total, the study included 22 patients, mainly males, with a mean age of 60 years. The lag from the onset of symptoms of COVID-19 to development of skin manifestations was relatively short, 3 days (range, 2 to 12 days). Most patients presented with the full clinical manifestations of the disease, with general and respiratory manifestations.19

Vesicular lesions, usually monomorphic, appear early on and may at times precede other symptoms (in 15% of patients),11 although in most cases, up to 79.2% in a series of 24 patents reported by Fernandez-Nieto et al.,20 they occur at the onset of other symptoms. There is involvement of the trunk in almost all cases and in 20% the limbs are also affected (Fig. 2). Exceptionally, facial and mucosal involvement have been reported. The skin lesions are barely symptomatic, but when they do cause symptoms, these are usually mild itching and, to a lesser extent pain or burning sensation.11,19 Although the lesions may be disperse, an extensive disseminated pattern is more frequent, 75% according to Fernandez-Nieto et al. In some patients, the legs may be affected, or the lesions may present with hemorrhagic content or be large, with a diffuse distribution. The mean duration of skin symptoms is 10.4 days (±9.3).11 In cases in which a biopsy was obtained, the findings were described as consistent with viral infection, showing vacuolar abnormalities and abnormal maturation of keratinocytes, as well as larger, multinucleated keratinocytes, and dyskeratosis.19 There have been no reports of presence of SARS-Cov-2 confirmed with positive PCR in biopsies of skin lesions.

Figure 2.

Disperse monomorphic papulovesicles on the trunk.

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Henry et al.21 reported the case of a female patient who developed an urticarial rash, accompanied by odynophagia and arthralgia, before developing the full clinical manifestations of COVID-19. Van Damme et al.22 reported a further 2 cases of urticarial rash as the first clinical manifestation of COVID-19, although microbiological confirmation of infection was only obtained in 1 of those, and in both cases the skin manifestations preceded pyrexia. One of the patients developed severe respiratory failure, leading to death.

Urticarial rash accounts for 19% of skin manifestations in COVID-19. In general, these skin manifestations become evident more or less at the same time as other general and respiratory symptoms. Lesions occur predominantly on the trunk, and involvement of the face and hands is frequent, with resolution in approximately 7 days.11 In one of the cases reported, histological study showed edema of the upper dermis and perivascular lymphocytic infiltration, with some eosinophils present.10 Although such lesions may be associated with worse prognosis in some patients,11 this is a nonspecific rash, and it has been reported in patients with a favorable clinical outcome and those with limited symptoms.23

There is probably a certain degree of variability in the way in which rashes are reported as urticarial maculopapular because, in the cases described, it is not specified whether the lesions follow a transient course or not. These are nonspecific rashes in which it is difficult to establish a solid relationship with viral infection, bearing in mind that the patients who present with these lesions have often received a range of treatments such as antiviral agents, antibiotics, hydroxychloroquine, anticoagulants, and support treatments, and these could also trigger skin reactions (Fig. 3). In fact, in a histological study, some cases of vacuolar interface dermatitis were observed with occasional necrotic keratinocytes, findings more reminiscent of a multiform erythematous pattern.24

Figure 3.

Maculopapular rash in a patient with COVID-19 associated with bilateral pneumonia, who received different drugs. Differential diagnosis with respect to toxicoderma is difficult.

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This group of lesions includes a heterogeneous group of rashes that, considered together, and given the difficulty of further subclassification, account for 47% of the skin manifestations in patients with COVID-19.11 At times, these rashes may be accompanied by a petechial component or with macules or more extensive areas with a purpuric appearance. In other cases, the lesions have a markedly perifollicular distribution (Fig. 4) with variable degrees of scaling, some of which have been reported as similar to pityriasis rosea.25 Infiltrated papules have also been observed; these are pseudovesicular lesions or similar to erythema elevatum diutinum or multiform erythema, and they may occasionally be pruritic (Fig. 5).26 A markedly craniocaudal development has also been reported, with involvement of the folds but without the palmoplantar region or the mucosa being affected.27,28

Figure 4.

Nonspecific rash, with perifollicular distribution in a patient with COVID-19.

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Figure 5.

Multiform erythema-like eruption in a patient with SARS-CoV-2 infection.

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Jimenez-Cauhe et al.29 reported the case of a female patient who developed a coalescent erythematous-purpuric rash about a millimeter in size, with a flexural distribution predominantly in the periaxillary region. The authors considered the difficulty of associating the skin manifestations with viral infection in view of its nonspecific appearance and concomitant medication use. Other authors have reported the appearance of rash that resembles the typical skin involvement of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), possibly associated with viral infection, given that the rash resolved despite continued use of the drug.30 We have also observed a similar distribution in our own patients (Fig. 6). From the histological point of view, a range of features have been reported within the group of maculopapular rashes, such as a perivascular inflammatory infiltrate with discrete lymphocytic exocytosis, marked vessel dilatation in the superficial and medial dermis, as well as lymphocytic vasculitis.31,32

Figure 6.

Periaxillary exanthematous eruption similar to SDRIFE.

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There is limited additional information in these patients regarding the timing with respect to other clinical manifestations or its prognostic or diagnostic value. In most cases, maculopapular rashes appear either at the same time as the characteristic respiratory symptoms or a few days later.11,28,32,33 However, in our hospital, we have detected more or less generalized maculopapular rashes, in some cases similar to multiform erythema, in young patients with a history of mild or even no symptoms, although with epidemiological evidence of infection with SARS-CoV-2 and these resemble those that can be seen in other viral infections.

Livedoid or necrotic lesions are relatively uncommon, accounting for 6% of skin lesions in the series reported by Galván et al.11 These are lesions usually reported in elderly patients with prior comorbidities and with severe forms of COVID-19 infection. They are considered secondary to vascular micro-occlusion and acral ischemia due to general deterioration in the patient's state and/or the coagulation disorders attributed to COVID-192,5 (Fig. 7).8 However, in some patients, episodes have been reported of patchy livedo reticularis that presented over the course of minutes or hours, of an uncertain nature and a benign course.35

Figure 7.

Livedoid rash with a transient course on the trunk of a patient with severe COVID-19.

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In the histological study of cutaneous purpuric lesions, a pauci-inflammatory thrombogenic vasculopathy has been found, with C5b-9 and C4d deposits, and localization of viral particles, leading to suspicion of the presence of a catastrophic microvascular lesion caused by complement activation.6