Histiocytic hyperplasia with hemophagocytosis and acute alveolar damage in COVID-19 infection.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

Non-infectious Uveitis as a Manifestation of the Immune Reconstitution Inflammatory Syndrome in Patients Infected by HIV.

OBJECTIVE: To describe a retrospective review of HIV patients with noninfectious uveitis. Data collected included: demographics, anatomic classification and phenotypic diagnosis of the uveitis, systemic immune-mediated disorders (IMD), time from HIV diagnosis to uveitis, CD4 count, viral load, treatment and complications of treatment and time of follow-up. RESULTS: Twenty patients (18 males) were included. The time lag between HIV diagnosis and the onset of uveitis was 9 ± 8.5 years. Mean CD4 count was 670 ± 294 cells/ml. Viral load was undetectable in 14 out of 18 cases. In 6 patients IMD was diagnosed prior to or concurring with the uveitis diagnosis. The use of immunosuppressive therapies was necessary in 6 patients (including biologics in 4 cases). The mean follow-up was 42.2 months. CONCLUSIONS: noninfectious uveitis could be the first manifestation of IMD in patients with well-controlled HIV infection. Immunosuppression appeared to be a safe therapeutic option in our cohort of patients.

Long term follow-up and effect of immunosuppression in acute zonal occult outer retinopathy.

Acute zonal occult outer retinopathy (AZOOR) is a rare syndrome characterized by sudden onset of photopsia, scotomas, and abnormal electrophysiological tests, predominantly affecting young women. Although its pathogenesis remains unknown, auto-reactivity to retinal components is thought to mediate tissue damage. A 42-year-old woman presented with symptoms and examination consistent with the diagnosis of AZOOR. She was treated with azathioprine for 5 years. In spite of the immunosuppressive treatment, clear progression in the visual field, autofluorescence, electrophysiological tests and optical coherence tomography was observed. Treatment with intravenous immunoglobulins (IVIg) and subcutaneous Abatacept was subsequently started with little efficacy. Hereby, we present a case of progressive AZOOR despite aggressive immunosuppression with 10-year follow up. Currently, there is no consensus regarding management of AZOOR, and the convenience of administering aggressive immunosuppression remains uncertain.

Ultrasound salivary gland involvement in Sjogren's syndrome vs. other connective tissue diseases: is it autoantibody and gland dependent?

This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer's test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0-3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0-12 and a parotid/submandibular score of 0-6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (p < 0.001) and significantly more SS patients showed a pathological global (p < 0.001), parotid (p < 0.001), or submandibular (p = 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer's test were associated with pathological US and higher scores at the submandibular level (p < 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD. KEY POINTS: • Patients with SS and other CTDs showed different grades of SGUS abnormality. • Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles. • Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.