A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection

Abstract

Background: Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet.

Objective: To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection.

Methods: Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy.

Results: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3.

Conclusions: Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

Figure 1

Clinical features. Erythema and swelling of right foot toes (a); erythema and swelling, particularly marked on the fourth right toe (b); purpuric macules, more evident on the second toe of both feet (c); erythema, mild swelling and multiple crusts on left toes (d).

Figure 2

Clinical features. Diffuse swelling, erythema and crusts on the left foot, and two pustules (arrows) on the big toes (a); purpuric macules on the lateral aspect of the right heel (b); confluent purpuric macules mostly covered by crusts on both heels and posterior ankles (c); brownish purpuric macules on the soles (d).

Figure 3

Videocapillaroscopy findings. Multiple and synchronous microhaemorrhages (asterisks), pericapillary oedema (arrows) on the finger nailfold (a); abnormal morphology of the capillaries (Black circle) and pericapillary oedema (arrows) on the toe nailfold of the same patient (b). Pericapillary oedema (arrows), dilated capillaries (Black triangle) and abnormal capillary morphology (Black circle) on the finger nailfold (c); numerous and prominent microhaemorrhages (asterisks), marked abnormal capillary morphology (circles) and pericapillary oedema (arrows) on the toe nailfold of the same patient (d).

Figure 4

Histopathological findings. Representative low‐power magnification of a punch skin biopsy showing perivascular inflammatory infiltrate in the superficial and deep dermis and subcutaneous tissue (a); higher magnification of the arteriole indicated with an arrow in (a) shows an intramural lymphocytic infiltrate (b); a scale‐crust, epidermal spongiosis, basal layer smudging (arrow) and oedema of papillary dermis with extravasated erythrocytes are evident in (c); a dermal capillary blood vessel with intraluminal thrombus is visible in (d); dense perieccrine and perineural dermal inflammatory infiltrate associated with mucin deposits (e) highlighted by Alcian blue staining shown in (f). a–e: Haematoxylin–eosin staining; bars: 500 µm in a; 50 µm in b and d; 100 µm in c, e and f.

Figure 5

Direct immunofluorescence findings. Granular deposits of C3 in the wall of vessels (asterisk) in the papillary and deep dermis (a and b, respectively) and focal deposits along the dermal–epidermal junction; colloid bodies at the dermal–epidermal junction staining positive for IgM (c). Bars: 50 µm in a and b; 100 µm in c.

Figure 6

Ultrastructural features. Extravasated red blood cells (R) are visible in an oedematous (asterisks) papillary dermis (a, ‘F’ denotes two fibroblasts); a dermal infiltrate chiefly composed of small to medium size lymphocytes (L) is observed in the papillary dermis (b); protruding endothelial cells with prominent intraluminal nuclei, one with condensed chromatin (asterisk in c), line two dermal vessels (c and d), one showing partly denuded and interrupted basement membrane (asterisk in d). Bars: 10 µm in (a) and (b), 5 µm in (c) and (d).