INTRODUCTION
Erythematous patches or swollen plaques appearing usually after 4 days or more at the injection site of SARS‐CoV‐2 vaccination are commonly known as ‘COVID‐Arm’. 1 It is considered normal to have signs of inflammation up to 3 days after the vaccine is administered. Pathological inflammatory reactions are those that persist beyond 3 days. COVID‐Arm is one of the most commonly reported adverse effect of all COVID‐19 vaccines, but it seems much more frequent with mRNA‐1273. 2 , 3 , 4 COVID‐Arm is almost exclusively described in women. 5 Skin biopsies in COVID‐Arm have shown superficial perivascular and perifollicular lymphocytic infiltrates, with rare eosinophils and scattered mast cells. These findings correspond with a delayed‐type hypersensitivity reaction. 6
High‐frequency ultrasound (HFUS) 7 aids in the diagnosis and follow‐up of inflammatory skin diseases. 8 We describe herein the ultrasound characteristics of local injection‐site cutaneous adverse reactions after vaccination against SARS‐CoV‐2.
PATIENTS
We studied seven patients with COVID‐Arm attended in our department between the 1st of March and the 30th of June, 2021. All patients were Caucasian females, with age between 27 and 59 years (median, 37 years). We excluded patients with injection‐site reactions lasting ≤3 days, as this reaction was very common in SARS‐CoV‐2 vaccine randomised controlled trials. 9
The study was authorised by the Ethics Committees of our institution. All patients gave written informed consent to participate and explicit consent to publish images.
TECHNIQUE
HFUS was performed by a dermatologist trained in the diagnosis and management of autoimmune diseases and HFUS. Esaote MyLab™Class C equipment was used with high‐frequency probes between 10, 18 and 22 MHz.
The following cut‐off values were used to determine negative Doppler: isolated vessels in the dermis and hypodermis, with a systolic peak of <10 cm/s and a resistance index of <0.7. 2 , 10 Active panniculitis was defined as fulfilment of ≥2 of the three criteria in Doppler mode: systolic peak >10 cm/s, resistance index >0.7 MHz, and vessel diameter >1 mm.
The variables analysed in mode B of the HFUS considered to be indicative of inflammation were hypoechogenicity of the dermis, hyperechogenicity of lobes in all cases with or without hypoechogenicity and thickening of the subcutaneous septa. 3 , 8 Increased or decreased echogenicity was considered in comparison with healthy perilesional and contralateral skin. Septa were considered thickened if 3 or more septa were thicker than 1 mm. 10 Other signs present in active disease were hypoechogenicity of the dermis and loss of the dermo‐hypodermal line. 8
RESULTS
Table 1 shows the clinical and HFUS characteristics of patients. In one patient, localised inflammation was observed only in the dermis, without signs of panniculitis (Figure 1). Inflammation of the hypodermis was observed in six of the seven patients (85.7%); in five (71.4%) cases, the ultrasound pattern was lobular panniculitis and in only one (14.3%) was mixed panniculitis (septal and lobular). Vessel diameter was increased, with a median of 1.4 mm (IQR: 0.8−1.7 mm), and a median peak systolic velocity of 7 cm/s (IQR: 5−15.2 cm/s) (Figures 2, 3, 4).
Table 1.
Clinical and high‐frequency ultrasound characteristics of patients
| Case | Age | Medical history | Dose | Day of onset | Duration | Systemic symptoms | Treatment | US findings |
|---|---|---|---|---|---|---|---|---|
| 1 | 37 | Depression | 2nd (selfreported also for 1st dose) | 1 | 10 | Fever | Topical corticosteroids—oral antihistamines | Hypoechoic dermis. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules and hypoechogenicity of the septa. Doppler with an intense increase of flow in dermis and hypodermis: arterial vessels of 1.2 mm diameter and high velocity compared to healthy skin, with a systolic peak of 9 cm/s and a resistance index of 0.71. |
| 2 | 27 | No | 1st | 4 | 7 | Nausea, diarrhoea, headache painful lymph node | Topical corticosteroids—NSAIDs | Hypoechoic dermis. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules. Doppler with an intense increase in flow in dermis and hypodermis: arterial vessels of 1.4 mm in diameter and a high velocity compared to healthy skin, with a systolic peak of 7 cm/s and a resistance index of 0.70. |
| 3 | 37 | No | 1st | 5 | 10 | Painful lymph node | Topical corticosteroids—NSAIDs | Hypoechogenicity of the dermis with an intense increase of flow in Doppler mode, fine arterial vessels of low velocity systolic peak 5 cm/s. Preservation of dermo‐hypodermal differentiationHypodermis of normal appearanceEnlarged lymph node: 20.1 × 9.3 mm, with intense vascularisation in the hilum towards the periphery; with arterial vessels up to 1.2 mm in diameter and a very high velocity: the systolic peak of 37.2 cm/s and resistance index of 0.87. |
| 4 | 59 | No | 1st | 6 | 8 | Headache, fever | Topical corticosteroids—oral antihistamines | Dermis with echogenicity similar to healthy skin. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules. Doppler with a mild increase of flow in dermis and hypodermis: arterial vessels of 1.2 mm in diameter and low velocity, with a systolic peak of 5 cm/s. |
| 5 | 30 | No | 1st | 8 | a | Asthenia | Paracetamol—topical corticosteroids | Hypoechogenicity of the dermis. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules. Doppler with an intense increase of flow in dermis and hypodermis: arterial vessels of 1.1 mm in diameter and high velocity compared to healthy skin, with a systolic peak of 15.2 cm/s and a resistance index of 0.77. |
| 6 | 33 | Hypothyroidism | 1st | 1 | 10 | Painful lymph node | No | Dermis with echogenicity similar to healthy skin. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules. Doppler with slightly increased flow in dermis and hypodermis: arterial vessels of 0.8 mm diameter and low velocity, with a systolic peak of 5 cm/s. |
| 7 | 52 | No | 1st | 7 | 14 | Headache, myalgia | Topical corticosteroids—oral antihistaminesParacetamol | Dermis with echogenicity similar to healthy skin. Loss of differentiation between dermis and hypodermis. Hyperechogenicity of the lobules. Doppler with the significantly increased flow in dermis and hypodermis: arterial vessels of 1.7 mm in diameter and high velocity, with a systolic peak of 10.6 cm/s and a resistance index of 0.73. |
Data not reported.
Figure 1.
Case 3. Hypoechogenicity and increased Doppler flow in the dermis.
Figure 2.
Case 1. Increased vascularisation in dermis and hypodermis. Arterial vessels with a 9 cm/s systolic peak, diastolic 2.6 cm/s, and a resistance index of 0.71.
Figure 3.
Case 1. Increased vascularisation in the hypodermis, with arterial vessels measuring 1.2 mm in diameter
Figure 4.
Case 5. Power Doppler Colour: increased vascularisation in dermis and hypodermis.
Areas of inflammation were observed with hypoechogenicity of the dermis and hyperechogenicity of lobules in the hypodermis. In addition, in patients with panniculitis, a loss of differentiation between dermis and hypodermis was seen. These findings can be seen in Figures 5 and 6, where the inflamed area is compared with the contralateral healthy skin.
Figure 5.
Case 4. (a) Healthy skin. d, dermis; sc, subcutaneous tissue; m, muscle. (b) Panniculitis: hypoechogenicity of the dermis and hyperechogenicity of the lining of the dermis.
Figure 6.
Case 6. (a) Panniculitis: loss of differentiation between dermis and hypodermis. (b) Healthy skin. d, dermis; sc, subcutaneous tissue; m, muscle.
In one patient, an enlarged axillary lymph node was observed on the same side of the vaccine application. The node measured 20.1 x 9.3 mm with intense vascularisation distributed from the hilum towards the periphery, had arterial vessels up to 1.2 mm in diameter and a very high velocity (a systolic peak of 37.2 cm/s and resistance index of 0.87) (Figure 7). A characteristic HFUS pattern of inflammation was observed in this patient, with increased flow from the hilum to the periphery.
Figure 7.
Case 3. High‐frequency ultrasound pattern of inflammation in an enlarged lymph node.
DISCUSSION
We observed that patients with COVID‐Arm had inflammation of the dermis and the hypodermis, with signs of panniculitis, similar to those seen with HFUS in autoimmune and infectious diseases. 10 The colour Doppler mode allowed us to quantify the inflammation and indicate treatment according to clinical and ultrasonographic signs. In addition, other findings such as inflammatory lymph nodes were observed.
COVID‐Arm is usually diagnosed on clinical grounds. 1 In most cases, inflammation resolves spontaneously or with topical anti‐inflammatory treatment after a few days. 2 Therefore, skin biopsy is usually not necessary. Some patients may have persistent lesions that require longer topical treatment or even oral corticosteroid therapy.
HFUS is a technique that has become widespread in a routine dermatology practice in recent years. 10 It can be carried out at the office and aids in therapeutic decision making, by comparing clinical and imaging findings. In inflammatory diseases, HFUS is helpful to define the site of involvement (whether dermal, hypodermic, or both) and quantify vascularisation. 8 , 10 In panniculitis, HFUS has proven helpful in assessing lobular, septal, or mixed patterns. Finally, HFUS permits assessment of response to treatment during follow‐up.
In our case series, COVID‐Arm affected the deeper layers of the skin. This was demonstrated with HFUS, without the need for a skin biopsy. We propose that HFUS is a useful noninvasive imaging technique for a complete assessment of vaccine reactions.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ETHICS STATEMENT
The study was authorized by the Ethics Committees of our institution. All patients gave written informed consent to participate and explicit consent to publish images.
ACKNOWLEDGEMENTS
We thank the Pharmacovigilance and Occupational Health departments and technical committee of the Hospital Clinic of Barcelona for their generous contributions. This study forms part of the PhD degree of Alba Català, Department of Medicine, Dermatology, Universitat Autónoma de Barcelona, Spain; and PhD degree of Priscila Giavedoni, Department of Medicine, Dermatology, Universitat de Barcelona, Spain.
Giavedoni P, Català Gonzalo A, Gómez‐Armayones S. Sonographic findings of COVID‐Arm: a case series. JEADV Clin Pract. 2022;1:450–456. 10.1002/jvc2.49
[Correction added on 5 November 2022, after first online publication: Ethics statement has been added.]
Priscila Giavedoni and AlbaCatalà Gonzalo contributed equally to this study.
DATA AVAILABILITY STATEMENT
Materials, data, and associated protocols are available upon request to readers.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Materials, data, and associated protocols are available upon request to readers.