Acute Endotheliitis (Type 3 Hypersensitivity Vasculitis) in Ten COVID-19 Autopsy Brains

Central nervous system (CNS) involvement in COVID-19 may occur through direct SARS-CoV-2 invasion through peripheral or cranial nerves or through vascular endothelial cell infection. The renin-angiotensin system may play a major part in CNS morbidity. Effects of hypoxia have also been implicated in CNS lesions in COVID-19. This communication reports on ten consecutive autopsies of individuals with death due to COVID-19 with decedent survival ranging from 30 minutes to 84 days after admission. All ten brains examined had neutrophilic microvascular endotheliitis present in variable amounts and variably distributed. Importantly, this acute stage of type 3 hypersensitivity vasculitis can be followed by fibrinoid necrosis and inner vascular wall sclerosis, but these later stages were not found. These results suggest that a vasculitis with autoimmune features occurred in all ten patients. It is possible that viral antigen in or on microvascular walls or other antigen-antibody complexes occurred in all ten patients proximate to death as a form of autoimmune vasculitis.

Educational Case: Hypersensitivity Vasculitis

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1

Renal Involvement in IgA Vasculitis; Possible Correlation with Positive Antiphospholipid Antibodies

IgA vasculitis is a hypersensitivity vasculitis, which is usually self-limiting. Renal involvement is the most damaging long-term complication of IgA vasculitis, happening in 20% - 100% of cases. Some factors have been reported to be associated with renal involvement in IgA vasculitis; however, no biomarker has been proved as a risk factor for renal involvement and its severity yet. We followed 48 patients with a confirmed diagnosis of IgA vasculitis for six months. We checked these patients for renal involvement by microscopic urine examination. We checked aPL antibodies in all patients on admission and 12 weeks later. Urinalysis showed renal involvement in 14 of 48 patients with IgA vasculitis (29.16%). Antiphospholipid antibodies were positive in 9 patients with IgA vasculitis and renal involvement (9 out of 14, 64.28%), while they were positive in only six patients with IgA vasculitis without renal involvement (6 out of 34, 17.64%), showing a moderate correlation between positive aLP and renal involvement in patients with IgA vasculitis, with a kappa index of 0.457. Serum aPL antibodies, as a tool to predict renal involvement in IgA vasculitis, show a sensitivity of 64.3%, a specificity of 82.4%, PPV of 60.0%, and NPV of 84.8%, demonstrating that a positive serum aPL antibody can be used to positively predict the renal involvement, while a negative result is not strong enough to rule out future renal involvement.

Eosinophilia

Eosinophilia (eosinophil count >0.45 × 109/litre) is associated with some infections, some allergic diseases, and a variety of other conditions, sometimes neoplastic. Parasitic diseases—eosinophilia is a characteristic feature of infection by multicellular helminth parasites (e.g. Strongyloides stercoralis) with diagnosis typically based on geographical/dietary history, serological tests, and examination of stool or tissues for parasite forms. Other diseases—eosinophilia can be caused by the fungal disease coccidioidomycosis, and modest eosinophilia may accompany retroviral infections such as HIV and HTLV-1. Common allergic diseases—asthma, rhinitis, and atopic dermatitis are associated with modest eosinophilia. Drug reactions—these are a frequent cause of eosinophilia, at times in reactions characterized by rashes and pyrexia. More severe reactions may also manifest with (1) pulmonary eosinophilia and lung infiltrates; (2) interstitial nephritis; (3) hepatitis; (4) myocarditis; (5) drug-induced hypersensitivity vasculitis; (6) gastroenterocolitis; and (7) DRESS syndrome. Other conditions—these include (1) eosinophilic granulomatosis with polyangiitis; (2) hyper-IgE syndromes; (3) chronic myeloid leukaemia, acute myeloid leukaemia, and lymphoma; (4) a variety of pulmonary, skin, gastrointestinal, and endocrine diseases. Hypereosinophilic syndromes are defined by (1) eosinophilia (>1.5 × 109/litre) sustained over a month, (2) lack of an identifiable cause precipitating a secondary eosinophilia, and (3) symptoms and signs of organ involvement. About 30% of patients will have either a myeloproliferative condition (chronic eosinophilic leukaemia) or hypereosinophilia mediated by clonal expansion of specific T cells producing interleukin-5 (IL-5). Treatment—patients without organ damage do not require treatment. Aside from supportive care, chronic eosinophilic leukaemia may respond to tyrosine kinase inhibitors (e.g. imatinib), and nonmyeloproliferative hypereosinophilic syndrome may respond to high-dose corticosteroids, with hydroxyurea, interferon-α‎ or anti-IL-5 monoclonal antibody used in refractory cases.

A Unique Case Report on Hypersensitivity Vasculitis as an Allergic Reaction to the Herpes Zoster Vaccine

Hypersensitivity vasculitis (HV) or leukocytoclastic vasculitis is a rare small-vessel vasculitis that may occur as a manifestation of the body’s extreme allergic reaction to a drug, infection, or other foreign substance. Characterized by the presence of inflammatory neutrophils in vessel walls, HV results in inflammation and damage to blood vessels, primarily in the skin. Histologically, when neutrophils undergo leukocytoclasia and release nuclear debris into the vasculature, vascular damage manifests as palpable purpura. The incidence of HV is unknown and its relationship and interaction with certain vaccinations is rare and poorly understood. Affected patients with HV generally have a good prognosis; however, fatality may occur if organs such as the central nervous system, heart, lungs, or kidneys are involved. We report a unique case of a 60-year-old man who presented with a serious case of HV after receiving the herpes zoster vaccine. A thorough literature review yielded only one similar case of vascular reaction to the varicella vaccine that was reported in the Annals of Internal Medicine in 1997; however, no other reported cases with regard to the herpes zoster vaccine have been found. Our case presents a rare glimpse into HV that may result from varicella vaccine administration.

CLOPIDROGEL INDUCED LEUKOCYTOCLASTIC VASCULITIS

Cutaneous adverse drug reactions are very common in a hospital setting while treating patients. Drug-induced vasculitis is a very common form of vasculitis affecting all age groups, and many drugs have been implicated in causing vasculitis. Clopidogrel is an antiplatelet drug used in the management as well as prevention of coronary artery disease. It is known to cause various side effects ranging from bleeding, gastrointestinal disturbances, to skin rashes. Leukocytoclastic vasculitis is a form of hypersensitivity vasculitis and is very rarely seen with clopidogrel. Hence, we report a case of clopidogrel-induced leukocytoclastic vasculitis in an old male patient after coronary stenting.