Cutaneous histopathology of Rocky Mountain spotted fever

Abstract

The dermatologic diagnosis of Rocky Mountain spotted fever (RMSF) is often presumptive; the clinical presentation includes skin rash and febrile illness with or without a clear history of tick bite. The characteristic cutaneous manifestations include a generalized skin eruption with purpuric, blanching or non-blanching macules and papules usually involving the extremities. Although skin biopsies are often performed to confirm the diagnosis, the spectrum of cutaneous histopathology in RMSF has not been well described. We studied a series of 26 cases of RMSF, of which 10 were surgical specimens and 16 were autopsies. The microscopic changes were correlated with the duration of illness. The main histopathologic feature was lymphohistiocytic capillaritis and venulitis with extravasation of erythrocytes, edema, predominantly perivascular and some interstitial infiltrate. Leukocytoclastic vasculitis (LCV) with neutrophilic infiltrate and nuclear dust was seen in 11 of 15 (73%) specimens from involved skin. These lesions with LCV also showed notable epidermal change including basal layer vacuolar degeneration with mild dermoepidermal interface lymphocytic exocytosis. Six lesions with LCV displayed focal fibrin thrombi and capillary wall necrosis. Apoptotic keratinocytes were noted in 3 lesions with LCV. Subepidermal blister was observed in the skin lesion of an autopsied patient with LCV changes. Another lesion of a fatal case with LCV also contained features of acute neutrophilic eccrine hidradenitis. Focal small nerve twig inflammation was noted in a third autopsy case with LCV. Plasma cells were seen in 6 of 34 specimens (18%); and eosinophils were observed in 3 (9%). The subcutaneous fat contained a mild perivascular inflammation and one case revealed focal lobular neutrophilic inflammation. Immunohistologic (IH) staining using polyclonal rabbit anti-Rickettsia rickettsii demonstrated positive staining of the organisms in the affected endothelial cells in all 12 cases tested. The cutaneous histopathology of RMSF is caused by endothelial damage by the rickettsial organisms which elicit an initial lymphohistiocytic small vessel vasculitis with progression to LCV. The vasculitis in RMSF is, therefore, considered to be a form of septic vasculitis.

Anti-Protective Antigen IgG Enzyme-Linked Immunosorbent Assay for Diagnosis of Cutaneous Anthrax in India

“…Skin infection begins as a raised itchy bump that resembles an insect bite but within 1 to 2 days develops into a vesicle and then a painless ulcer. Cutaneous anthrax is characterized by the formation of a black eschar surrounded by prominent edema and vesicles, which may resemble many other skin lesions, such as ulceroglandular tularemia (21), plague (12), ecthyma gangrenosum (8), various spotted fever group rickettsial infections (10), and scrub typhus (3). The clinical diagnosis of cutaneous anthrax is traditionally established by microbiological methods like demonstrating Gram-positive, capsulated bacilli on the smear of the lesion or isolating B. anthracis in culture (2,24).…”

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

“…By analogy with Rocky Mountain spotted fever, endothelial cells are considered the key target cells. [2][3][4][5] However, it is not known whether organisms deposited in the skin spread to internal organs via the circulation, the lymphatics, as naked bacilli, or by another mechanism. A standard method for isolating O. tsutsugamushi from infected humans is to inoculate peripheral blood into mice at the bedside, 6 implying that organisms are present in the circulation.…”

Fiebre manchada por Rickettsia rickettsii en las Américas: un problema creciente de salud pública

“…Las complicaciones más severas de la infección por R. rickettsii son secundarias a la rápida diseminación sistémica de la bacteria a través de la microvasculatura 56,57 . En el interior de la célula endotelial, R. rickettsii se ancla al citoesqueleto de actina a través del dominio WH2, una secuencia conservada evolutivamente en las proteínas WASP (proteínas relacionadas con el Síndrome de Wiskott-Aldrich que controlan la polimerización de actina), de la proteína de superficie RickA, la cual activa a Arp 2/3 (proteínas relacionadas a actina 2/3).…”

“…Las células del sistema inmunológico (principalmente células T y macrófagos), activadas por componentes de la microcápsula del agente, llegan al sitio de infección y liberan citosinas pro-inflamatorias (v.gr. interferón-γ, Interleucina-1 e Interleucina-6, entre otras) así como factores vasodilatadores como la histamina y el óxido nítrico, que inducen la liberación del factor de von Willebrand (FvW), proteína procoagulante contenida en el interior de los cuerpos de Weibel-Palade 5,60 , contribuyendo con ello a los daños orgánicos propios de la fiebre manchada 56 .…”