Histometric studies on biopsies of tuberculin skin tests showing evidence of ischaemia and necrosis

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Abstract
In a study of tuberculin skin tests in 216 consecutive untreated pulmonary tuberculosis patients, one showed central necrosis at 48 h: there was no effective blood flow at the centre of this lesion, but the periphery was markedly hyperaemic. Many dermal capillaries and venules contained deposits of fibrin, but none was occluded completely: the surviving cells in the dermal infiltrate were almost all macrophages. Five patients with strongly positive reactions at 48 h showed slower blood flow at the centre of the reaction than at the periphery (central relative slowing, CRS), possibly indicating central ischaemia short of necrosis: no fibrin deposits were seen in the dermal vessels of these skin test sites. The cellular infiltrate in the dermis was similar in distribution, but more abundant than that seen in uncomplicated positive reactions of comparable clinical size and with blood flow velocity maximal at the centre. At 48 h, lymphocytes were more numerous than macrophages in both groups, CD8 lymphocytes were more abundant in CRS reactions, but CD4 and CD25 (activated) T-lymphocytes and macrophages had a similar density in both groups. Epidermal CD1 cells were less frequent in CRS reactions than in uncomplicated positive reactions. Although CRS reactions showed more intense inflammation than the uncomplicated controls, none of the histometric measurements correlated with the extent of CRS. Follow-up studies showed that CRS reactions reverted to a normal hyperaemic blood flow pattern 5 days after antigen injection. Thus, relative ischaemia may arise temporarily in intense delayed hypersensitivity reactions during the early developing phase when compensatory hyperaemia is unable to match metabolic demand, but the tissue will survive for a few days provided the vessels are not occluded by fibrin.