Vascular injury in macroscopically normal skin of patients with severe COVID-19 infection: clinical-pathologic correlations

Objectives: Taking into account that the documentation of the histopathological features in severe disease caused by SARS-CoV-2 has been scarce due to the avoidance of performing autopsies, the aim of the study was to detect the microscopic changes associated with severe COVID-19 infection in normal-appearing skin, without prominent dermatologic signs of a generalized microvascular thrombotic disorder, in accordance with the clinical evolution of disease. Methods: In this morphological and immunohistochemical study we included cutaneous biopsy samples from 12 symptomatic patients with severe and critical type SARS-CoV-2 infection (with the admission date between February and June 2020), treated in the Intensive Therapy Unit Care of Emergency County Hospital Targu-Mures, Romania. Results: The average age of our patients was 65.18 ± 14.21 years (range 41 to 83), and 66.67% of the patients were male. The histological and immunohistochemical assessment of cutaneous biopsies: in 4 cases the histological examination revealed small fibrin thrombi in deep-seated venules and small veins of subcuticular adipose tissue, and also 4 cutaneous biopsies showed occlusive vascular thrombosis in association with massive perivascular inflammatory infiltrate destroying and compromising the integrity of the vessel wall. The immunohistochemical examination of the composition of perivascular inflammatory infiltrate showed a predominance of CD3 positive lymphocytes, admixed with CD68 positive Mo/ MF, some of them activated with FXIII expression. In the perivascular infiltrate, the presence of granulocytes and B lymphocytes was not characteristic. Conclusion: According to our observations, in severe COVID-19, the cutaneous tissue is involved even in the absence of clinically obvious changes. Due to the relatively easy accessibility of skin samples, these could be applied to determine the severity of the patient’s clinical status, and to predict the necessity for anti-complement or anticoagulant treatments in the early stages of a severe SARS-CoV-2 infection.

Comparative Analyses of Clinical Features, Histopathology, and CD123 Immunohistochemistry of Oral Lupus Erythematosus, Lichen Planus, and Other Lichenoid Lesions

<b><i>Background:</i></b> Oral lupus erythematosus (OLE) and oral lichen planus (OLP) are among the common causes of oral lichenoid lesions (OLLs). The differential diagnosis among causes of OLLs, particularly between OLE and OLP, is challenging as they have significant clinical and histopathological overlap. <b><i>Objectives:</i></b> To compare and summarize the clinical, histopathological, and direct immunofluorescence (DIF) findings between OLE, OLP, and other OLLs and to explore the diagnostic value of CD123 immunohistochemistry. <b><i>Methods:</i></b> A retrospective study on patients with OLE, OLP, and other OLLs was performed between January 2014 and December 2019. The baseline characteristics, the clinical, histopathological, and DIF features, as well as CD123 immunohistochemistry for plasmacytoid dendritic cells (PDCs) were statistically analyzed and compared between groups. <b><i>Results:</i></b> Of 70 patients, 12 had OLE, 39 had OLP, and 19 had other OLLs. Oral erosions/ulcers were the most common findings in all three groups. Red macules, telangiectases, and discoid plaques were more common in OLE patients, while OLP cases were typified by reticulated patches (<i>p</i> &#x3c; 0.05). Additionally, white patches were found more often in other OLLs than in both OLE and OLP (<i>p</i> = 0.002). Histologically, mucosal atrophy, basal vacuolization, and perivascular infiltrate were observed in OLE, whereas OLP specimens possessed mucosal hyperplasia, hypergranulosis, and compact orthokeratosis (<i>p</i> &#x3c; 0.05). Mucosal spongiosis was a histologic feature that favored other OLLs over OLE and OLP (<i>p</i> &#x3c; 0.001). Data on DIF were nonspecific for all three conditions. For immunohistochemical staining, the median number of total CD123+ PDCs was observed to be higher in OLE than OLP in the mucosal-submucosal junction (MSJ) (<i>p</i> = 0.021), the superficial perivascular area (<i>p</i> = 0.026), and the superficial and deep perivascular areas (<i>p</i> = 0.001). Likewise, PDCs in clusters ≥2+ were seen in significantly higher numbers on OLE than OLP along the MSJ (<i>p</i> = 0.002), the superficial perivascular area (<i>p</i> &#x3c; 0.001), as well as the superficial and deep perivascular areas (<i>p</i> = 0.011). CD123+ PDCs were found to be significantly more numerous in both OLE and OLP than other OLLs in all of the abovementioned areas (all <i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> While there are some differences in the clinicopathological features between OLE, OLP, as well as other OLLs, a significant overlap remains. The quantity and distribution pattern of CD123 immunohistochemical staining has a diagnostic implication in differentiating OLE from OLP and other OLLs.

Eosinophil rich infiltrate in secondary syphilis a rare histopathological variant

<p class="abstract">Secondary syphilis is a sexually transmitted infection, which is referred to as “the great imitator” and has a wide spectrum of clinical manifestations. Syphilis is classically associated with plasma cells and the presence of eosinophils usually argues against a diagnosis of syphilis. The differential diagnosis for eosinophil-rich skin lesions often includes a drug reaction, arthropod-bite reaction, allergic contact dermatitis, and a response to a helminth infestation. However, many unrelated entities, such as infections, neoplasms, and inflammatory dermatoses can have prominent eosinophilic infiltrate. We report a case of secondary syphilis which on histopathology showing psoriasiform hyperplasia with superficial perivascular infiltrate and on higher magnification these infiltrate were predominantly lymphohistiocytic along with the moderate amount of eosinophils with a paucity of plasma cells. This case report is presented to highlight the need for including secondary syphilis as one of the differential diagnoses in the presence of eosinophil-rich infiltrate when it is suspected clinically.</p>

Clinical Cutaneous Features of Patients Infected With SARS-CoV-2 Hospitalized for Pneumonia: A Cross-sectional Study

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a current pandemic worldwide. This virus can reach all organs and disturbs the immune system, leading to a cytokine storm in severe forms. We aimed to report cutaneous features among coronavirus disease 2019 (COVID-19) hospitalized patients. Methods We performed a cross-sectional study on 1 given day among all patients hospitalized in acute care for COVID-19 and included all patients with cutaneous features. Follow-up 48 hours later was obtained. Results Among 59 adult patients hospitalized on the day of the study in an infectious diseases ward for SARS-CoV-2 infection who were confirmed by molecular assay and/or radiological findings (computed tomography scan), 40 were included. Several cutaneous manifestations were found: macular exanthema (80%), face edema (32%), livedo (13%), urticarial rash (8%), purpura (5%), oral lichenoid lesions (33%), and conjunctivitis (18%). Cutaneous biopsy was performed in 17 patients. Histological findings showed mast cell hyperplasia (100%), superficial perivascular infiltrate of lymphocytes (94%), and superficial edema (47%) consistent with capillary leak. Conclusions Various dermatological signs can be encountered during COVID-19. A macular rash was the most frequent. All cutaneous features could be related to a vascular leak process.

Histopathological features of Chilblain-like lesions developing in the setting of the COVID-19 pandemic

Context: During the coronavirus disease 2019 pandemic, several studies have described a distinctive cutaneous manifestation with a clinical picture resembling chilblains or chilblain lupus in young patients. Objective: To report the histopathological description of a series of chilblain-like lesions appearing in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. Design: The study included 13 patients with cutaneous acral lesions resembling chilblains occurring in the setting of suspected SARS-CoV-2 infection with available skin biopsy. Results: Two main histopathological patterns were observed: a chilblain-like histopathological pattern (10 cases out of 13, 77%) and a thrombotic vasculopathy pattern (3 cases out of 13, 23% of cases). The chilblain-like histopathological pattern featured a superficial and deep perivascular infiltrate of lymphocytes of varying intensity. This infiltrate was sometimes peri-eccrine and alterations of eccrine glands were present in most cases. Vacuolar alteration of the basal layer of the epidermis was found in a majority of patients. Lichenoid interface dermatitis was rarely present. The thrombotic vasculopathy pattern featured an absent or mild inflammatory infiltrate, multiple intraluminal fibrin thrombi and ischemic epidermal necrosis. In both patterns, no true vasculitis was observed. No patient was tested positive for SARS-CoV-2 by polymerase chain reaction possibly due to the fact that these lesions may represent late cutaneous manifestations of the disease or are associated with an early effective immune response. Conclusion: The relationship of chilblain-like lesions to SARS-CoV-2 requires further investigations. Histopathological features mimic chilblains, chilblain lupus and less frequently a thrombotic vasculopathy. Response to viral infection might trigger diverse mechanisms leading to the two histopathological patterns described.

Erythema Dyschromicum Perstans

Erythema dyschromicum perstans is an asymptomatic eruption of oval, polycyclic, or irregularly shaped, gray-blue hyperpigmented macules on the trunk, the arms, the face, and the neck. It begins as ash-colored macules, sometimes with an erythematous or elevated border. The patient is not usually suffer from any systemic symptoms. Erythema dyschromicum perstans may resolve in 2-3 years in prepubertal children, but it is more likely to persist in adults. [1] Erythema dyschromicum perstans (EDP) most often affects darker skinned patients, most frequently Latin Americans and Indians. It has also been reported in people of lighter skin colour and various ethnicities. It may occur in women more often than men. It is repoted in young adults than adults. The exact etiology of EDP is unknown. Damage to melanocytes and basal cell keratinocytes that is observed with EDP is due to an abnormal immune response to antigens with a predominance of CD8 + T lymphocytes in the dermis and HLA-DR +, intercellular adhesion molecule 1 + keratinocytes in the epidermis. EDP is characterized in histological examination by a vacuolar liquefactive degeneration of the basal cell layer with dermal melanosis and a perivascular infiltrate.

Methotrexate-Associated Lymphoproliferative Disorder: Dermoscopic Features

Methotrexate-related lymphoproliferative disorder (MTX-LPD) is a rare disorder caused by long-term MTX therapy for autoimmune diseases. There has been no report of the dermoscopic features of MTX-LPD to date. A 64-year-old female presented with a slightly elevated indurated erythematous plaque with scales on her right thigh. The patient had been treated for rheumatic arthritis with MTX and prednisolone for more than 15 years, and 18 mg/week MTX without prednisolone had been administered in the last year. Dermoscopy revealed dotted vessels and glomerular vessels on pink homogeneous areas and multiple surface scales. Enhanced computed tomography showed multiple nodules and lymphadenopathies at the mediastinum and axillae. Histopathological examination revealed telangiectasia in the superficial dermis. Atypical lymphoid cells were scattered in the whole dermis and subcutaneous tissue. A perivascular infiltrate of atypical lymphocytes and histiocytoid cells partially destroyed the vessel walls. Epstein-Barr virus in situ hybridization showed a positive result. The cessation of MTX reduced the erythematous plaque, and lymphadenopathies at the neck, mediastinum, and axillae were not palpable. We discuss the relevance of these dermoscopic and histopathological features. The accumulation of such cases will reveal the dermoscopic features of MTX-LPD and the utility of dermoscopy for the diagnosis of MTX-LPD.

A Rare Presentation of Toxic Epidermal Necrolysis – Like Acute Systemic Lupus Erythematosus

A 25-year-old woman with a history of systemic lupus erythematosus (SLE) was transferred from an outside hospital with a worsening painful generalized rash and oral ulcerations for the prior 3 weeks due to concern for Stevens-Johnson Syndrome / toxic epidermal necrolysis (TEN). Exam revealed denuded erythematous plaques covering over 80% of the patient’s body surface area and a 4.2 x 2.6 cm ulcerated plaque of the superior hard palate. Histology demonstrated parakeratosis and compact hyperkeratosis overlying an atrophic epidermis with vacuolar interface change, prominent keratinocyte dyskeratosis, and a thickened basement membrane zone (BMZ). The superficial dermis had a mild predominantly lymphocytic perivascular infiltrate and superficial dermal mucin deposition. Direct immunofluorescence was positive for IgG (granular, BMZ), C3 (granular, BMZ), and IgA was negative. Labs were remarkable for positive ANA (1:160), ds-DNA, anti-Smith, anti-RNP, low C3/C4, with negative anti-SSA/SSB. The clinicopathological correlation was most consistent with the diagnosis of TEN-like acute systemic lupus erythematosus (TEN-like ASLE). Our patient improved with treatment for her ASLE. This case highlights a challenging clinicopathologic differential diagnosis.

Pruritic Vesicular Eruption on the Lower Legs in a Diabetic Female

A 50-year-old diabetic female presented with highly pruritic vesicles and excoriated lesions over the anterior aspect of both lower legs. The lesions were recurrent over the last two years. She received a lot of medications with partial response. Hb A1c was 10.8% (normal up to 7%). CBC showed microcytic, hypochromic anemia. Serum zinc, folate, IgE, TSH and T4 were all within normal ranges. Biopsy showed epidermal separation secondary to keratinocyte necrosis and minimal monocytic, perivascular infiltrate. Direct immunofluorescence was negative for intraepidermal and subepidremal deposition of immunoglobulin. The dermis was positive for mucin deposition stainable by both PAS and Alcian blue while it was negative for Congo red and APC immunoperoxidase staining for amyloid material. In conclusion, the case was diagnosed as bullosis diabeticorum by distinctive clinical and pathological features and after exclusion of other possible differentials. Pruritus was partially controlled by topical potent steroid and the case was resolved spontaneously after eight months.