IgA Vasculitis Associated With COVID-19.

IgA vasculitis, also known as Henoch-Schonlein Purpura (HSP), is an inflammatory disorder of small blood vessels that can present with palpable purpura, arthralgias, abdominal pain, and kidney disease. It is most commonly found in pediatric patients after an inciting infection but has been seen across all ages and associated with certain drugs and vaccines. COVID-19 has been associated with various cutaneous manifestations, but HSP is a rarely reported one. We present a case of a 21-year-old female presenting with a petechial rash found to be seronegative IgA vasculitis presenting concurrently with dyspnea secondary to COVID-19. She was initially seen by an outside practitioner, tested negative for COVID, and was prescribed a course of oral prednisone. Shortly thereafter, she visited the ED for worsening shortness of breath and tested positive for COVID-19, for which she received Paxlovid. Biopsy after a visit to a dermatologist confirmed intramural IgA deposition on immunofluorescence, and she was tapered off prednisone and started on azathioprine.

Histopathological Patterns of Cutaneous Adverse Reaction to Anti-SARS-CoV-2 Vaccines: The Integrative Role of Skin Biopsy.

The advent of vaccines represented a milestone to allow the slowing down and then containing of the exponential increase in ongoing infections and deaths of COVID-19. Since the first months of the vaccination campaign in various continents, there has been a certain number of reports of adverse events, including skin reactions. We conducted a systematic review, searching on PubMed, Web of Science, Scopus, and Cochrane Library for the words: COVID vaccine, dermatopathology, skin, eruptions, rash, cutaneous, BNT162b2 (Pfizer-BioNTech), ChAdOX1 (AstraZeneca), and mRNA-1273 (Moderna). A total of 28 records were initially identified in the literature search of which two were duplicates. After screening for eligibility and inclusion criteria, 18 publications were ultimately included. Various clinical cutaneous manifestations and histopathological patterns following vaccination have been described in literature. The most frequent clinical-pathological presentations were erythematous maculo-papular eruptions in different way of distribution with histopathological pictures mostly represented by interface changes and mixed peri-vascular and peri-adnexal cell infiltrate. Other presentations included new onset of pemphigoid bullous disease (n = 15), delayed T-cell-mediated hypersensitivity reaction (injection site reactions) (n = 10), purpuric skin rash (n = 13), mostly localized on the legs bilaterally and symmetrically with histological pictures characterized by extravasation of erythrocytes in the superficial and middle dermis, and other types of reactions. New studies with large case series and further literature reviews are needed to improve the clinical management of patients and optimize the timeline for carrying out histological biopsy for confirmatory, supportive, and differential diagnosis purposes.

SARS-CoV-2 and Skin: New Insights and Perspectives.

The SARS-CoV-2 pandemic has disrupted global health systems and brought the entire globe to its knees. Although born as a disease of the respiratory system, COVID-19 can affect different parts of the body, including the skin. Reports of ongoing skin manifestations of COVID-19 have gradually multiplied, pushing researchers to investigate the etiopathogenic mechanisms underlying these phenomena in more depth. In an attempt to investigate the possible association between SARS-CoV-2, ACE2, TMPRSS2 and skin manifestations, we performed immunohistochemical investigations of the ACE2 receptor and TMPRSS2 in nine skin samples from SARS-CoV-2-positive patients compared to a cohort of healthy controls. Furthermore, after consulting public databases regarding ACE2 mRNA expression in various cell populations resident in the skin, we conducted a literature review aimed at outlining the current state of this topic. We did not find statistically different immuno-expression of ACE2 and TMPRSS2 between the group of SARS-CoV-2-positive patients (nine skin biopsies) and the control group. Regarding ACE2, major immunolabeling was present in the epidermal keratinocytes and, rarely, in the fibroblasts and in the adenomeres of the eccrine sweat glands. Regarding the immune expression of TMPRSS2, we found no significant differences between the two groups, with a weak immune staining only in some skin cytotypes. From the review of the literature, we isolated 35 relevant articles according to the inclusion criteria adopted. ACE2 appears to be a target of SARS-CoV-2, although, other receptor molecules may potentially be implicated, such as TMPRSS2. Future studies with large cases and different molecular investigative methods are needed to further elucidate the mechanisms underlying the skin manifestations of SARS-CoV-2.

The Pathological Culprit of Neuropathic Skin Pain in Long COVID-19 Patients: A Case Series.

Cutaneous neurosensory symptoms have become increasingly reported findings in COVID-19; however, these virus-related manifestations are largely overlooked, and their pathology is poorly understood. Moreover, alterations of skin sensibility currently recognize no clear histopathology substrate. The purpose of this study was to provide pathology evidence of neurosensory skin system involvement in COVID-19 patients complaining of subjective neurological symptoms affecting the skin. Out of 142 patients, six long COVID-19 cases complaining of cutaneous subjective neurological symptoms assessed on an NTSS-6 questionnaire underwent histopathological and immunohistochemical analyses of skin areas affected by paroxysmal diffuse burning and itching sensations. Two patients also performed electroneurography examination. The histology investigation showed hypertrophic glomus vascular bodies with hypertrophic S100+ perineural sheath cells and adjacent hypertrophy of the nerve branches associated with increased basophil polysaccharide matrix. Electroneurography revealed disturbances of A-delta and C dermal neuronal fibers. The main limitation of this study consisted of a limited number of skin biopsy samples, requiring further investigation. Histopathology findings are consistent with hypertrophy of nerve endings, suggesting a condition such as "dermal hyperneury", a recently reported small nerve hypertrophy condition affecting sensory C fibers. Such a neuropathic basis could explain dysesthesia experienced by the patients, as previously described in postherpetic neuralgia.

Deferring Nail Mycological Sampling during the COVID-19 Pandemic: Recommendations from a Multidisciplinary Panel of Nail Specialists.

Onychomycosis is the most common nail condition seen in clinical practice, with significant impact on quality of life. Clinical examination alone is insufficient for accurate diagnosis, but mycological confirmation can be challenging during the COVID-19 pandemic. In this letter, a multidisciplinary panel of dermatologists, a podiatrist, dermatopathologists, and a mycologist, discuss considerations for mycological sampling during the pandemic.

Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: A registry-based study.

BACKGROUND: Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. METHODS: We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an international registry. When histopathology reports were available, we categorized them by reaction patterns. RESULTS: Of 803 vaccine reactions reported, 58 (7%) cases had biopsy reports available for review. The most common histopathologic reaction pattern was spongiotic dermatitis, which clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. We propose the acronym "V-REPP" (vaccine-related eruption of papules and plaques) for this spectrum. Other clinical patterns included bullous pemphigoid-like (n = 12), dermal hypersensitivity (n = 4), herpes zoster (n = 4), lichen planus-like (n = 4), pernio (n = 3), urticarial (n = 2), neutrophilic dermatosis (n = 2), leukocytoclastic vasculitis (n = 2), morbilliform (n = 2), delayed large local reactions (n = 2), erythromelalgia (n = 1), and other (n = 5). LIMITATIONS: Cases in which histopathology was available represented a minority of registry entries. Analysis of registry data cannot measure incidence. CONCLUSION: Clinical and histopathologic correlation allowed for categorization of cutaneous reactions to the COVID-19 vaccine. We propose defining a subset of vaccine-related eruption of papules and plaques, as well as 12 other patterns, following COVID-19 vaccination.

Papulo-purpuric dermatitis of childhood: a distinct PLEVA-like eruption associated to SARS-CoV-2 infection. Clinical, histopathological and immunohistochemical study of 10 cases.

We observed ten children with a papular eruption with purpuric features during the SARS-CoV-2 pandemic in Northern Italy (May-December 2020). Histological examination showed signs of SARS-CoV-2-related dermatosis. Evidence of nucleocapsid viral proteins using SARS-CoV-2 (2019-nCoV) nucleocapsid antibody revealed cuticular staining of the deep portion of the eccrine glands in all cases.

Histopathological findings in COVID-19-induced cutaneous lesions. Clinicopathological correlation of SARS-CoV-19 dermatologic patterns: review of the literature.

An increasing number of publications have brought attention to COVID-19-associated cutaneous lesions. Histopathological descriptions and clinical correlation of the histopathological findings of COVID-19 skin lesions are lacking. In this manuscript, we reviewed and described the histopathological characteristics of COVID-19 infection cutaneous patterns reported in the literature.

Chilblain-like acral lesions during the COVID-19 pandemic ("COVID toes"): Histologic, immunofluorescence, and immunohistochemical study of 17 cases.

BACKGROUND: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known. OBJECTIVE: To investigate the pathologic features of chilblain-like lesions. METHODS: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results). RESULTS: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels). CONCLUSIONS: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.

An outbreak of acute hemorrhagic papules on the posterior neck in children during the COVID-19 pandemic.

Within a two-week timespan in April 2020, multiple children presented with hemorrhagic macules, papules, and erosions localized to the posterior neck and occipital scalp. All of these patients were children of health care workers, with at least one confirmed COVID-19 exposure. The unique lesional morphology and the timing of onset led to SARS-CoV-2 antibody testing for all and biopsy of one child. Biopsy ultimately confirmed these lesions were consistent with arthropod bites, which coincided with an unprecedented surge in local populations of Simulium tuberosum, a biting gnat.