Periarteritis

Periarteritis, inflammation of the outer layer of arteries. As an isolated condition, it is observed very rarely and, conversely, almost always occurs in combination with changes to the inner and middle layers, which either precede the periarteritis, arise simultaneously with it, or quickly join it. Usually, the term periarteritis is used in cases where the main and most severe changes are concentrated in the outer layer, or when the process begins from it. Both of these can be observed primarily when any inflammatory process spreads to the vessel wall from surrounding tissue. This occurs in both acute (non-suppurative or suppurative) inflammation and in more slowly developing processes with a specific etiology (tuberculosis, syphilis, rheumatism, etc.), where very quickly after any damage to the adventitia, a proliferative reaction appears from the intima (see Endoarteritis), followed by thrombosis or without it, as well as necrobiotic changes in the muscular and elastic elements of the media, often with infiltration and vascularization of the latter, and subsequently with proliferation of connective tissue in it (see Mesarteritis). More acute and severe destructive processes when spreading to the vascular wall can cause rapid destruction of all its layers, leading to perforation and profuse (most often fatal) hemorrhages. Besides the spread of inflammation to the outer layer from surrounding parts, it can also be affected hematogenously in large and medium-sized arteries, i.e., through the vasa vasorum, and in these cases, changes to the outer and middle layers occur almost simultaneously, expressed in the first case mainly by infiltrative-proliferative processes, and in the second by necrobiotic changes. Proliferation of the intima immediately joins this. Such changes are very often observed in many acute and chronic infectious diseases. In small arteries, hematogenous periarteritis develops only sequentially (although often very rapidly) after damage to the inner and middle layers, if such damage is sufficiently intense and deep to either involve the adventitia in the destructive process (for example, in mycotic embolisms of small arteries by pus-forming microbes), or cause a proliferative reaction from it (as in acute non-suppurative arteritis of various infectious origins: scarlet fever, typhus, etc.). Among the hematogenous vascular lesions belonging to this group, a disease known as nodular periarteritis, periarteritis nodosa, deserves special attention.

M. Skvortsov. Nodular periarteritis is characterized by limited changes in the vascular wall in the form of nodules. As the process was studied, new names were proposed: polyarteritis, panarteritis, mesoarteritis, however, the name given first is most widely used, as it most aptly characterizes the external picture of the disease. First described in 1866 by Kussmaul and Maier; by 1931, approximately 200 cases had accumulated. The significant number in the last decade is explained more by increased interest in this disease than by its increased frequency. Nodular P. develops mainly in arteries of the muscular type, specifically in the arteries of organs, in their main trunks and more often on their branches down to small arteries and arterioles. As a rule, it is easily determined by the naked eye, but in the initial stage or with insignificant degree of changes or with exclusive involvement of arterioles, it can only be recognized microscopically. Macroscopically, along the course of the arteries, nodular, limited thickenings of round or oval shape, gray or yellowish-gray color, the size from poppy to millet grain or slightly larger, are noted. Less frequently, thickenings in the form of rollers or cylinders are encountered (mainly on large branches). The density of arrangement along the length of the vessel varies: sometimes closely one nodule to another in a chain-like fashion, sometimes only at the branching of vessels (especially small ones). On the surface of the vessel, the nodes clearly protrude, which is especially well seen on vessels located on the surface of an organ, e.g., on the coronary vessels under the epicardium. On the section of an organ, the nodes stand out distinctly and often thrombi are determined in the lumen of such vessels and aneurysms in the wall and hemorrhages into the surrounding tissue are noticeable. Microscopically, nodular P. consists of alteration, exudation, and proliferation, with fluctuations in the strength and predominance of one or another phase of inflammation; consequently, for a long time the site of origin of the process was controversial. At first, the adventitia was considered as such, and it was assumed that the other coats were involved sequentially; soon indications of primary changes in the muscular coat at its border with the adventitia appeared. Less frequently, indications of the primary process in the intima are encountered. At present, almost everyone recognizes the primary lesion of the muscular coat, and in small vessels without vasa vasorum, the changes begin in the inner layers of the muscular coat, while in large vessels with their own supplying vessels—in the outer layers of the muscular coat along the border with the adventitia. The first phase is the alterative one: necrosis, swelling and edematous impregnation of the muscular coat; to these changes the next phase—exudative—quickly joins: exudation of exudate containing fibrin along the border of the muscular and adventitial or muscular and intimal coats, on both sides of lam. elast. int.; at the site of damage, the muscular wall loosens, and the exudate, reaching the inner layers of the intima and endothelium, bulges them into the lumen of the vessel and exudes into it, sometimes with the formation of a mural thrombus. In addition, degenerative changes of the endothelium are also noted in the intima; but this phenomenon, according to Gruber, is secondary, occurring after changes in the muscular coat. In the adventitia, accumulation of cells occurs, first polymorphonuclear leukocytes, sometimes with a sharp predominance of eosinophils, and then ^: mononuclear lymphocytes, histiocytes, so that in the next proliferative phase, the nodule in the adventitia consists mainly of histiocytes. Plasma cells are rare. The cellular infiltrate spreads from the adventitia into the muscular and intimal coats; around vasa vasorum, cuffs of lymphoid infiltration are also observed [see separate table (pp. 567-568), Fig. 2]. Lamina elast. int. with severe damage to the muscular coat can be greatly stretched and even torn; regressive changes are also observed in it—poor and uneven staining, thickening, crumbliness and delamination. A strong degree of changes causes a sharp weakening of the wall, dilatations of the lumen, bulgings, ruptures with hemorrhages. Gradually, ordinary granulation tissue forms, which turns into a scar with remnants of the destroyed elastic membrane; deposits of hemosiderin are frequent. Scar tissue in large vessels often gives rise to dilatations, ruptures, tears and intramural hematomas; small vessels can become completely obliterated. The pathogenesis and etiology of nodular P. have been studied insufficiently. The view of nodular P. as an inflammatory process of infectious-toxic origin has received the greatest development and recognition. Some authors do not consider it possible to finally abandon the view of nodular P. as an independent systemic disease with an as yet unknown causative agent. Most consider the non-specificity of nodular P. proven; its cause can apparently be any infectious-toxic agent, which in some cases causes changes of the type described by Wiesel and Wiesner in various infectious diseases, in other cases—a complex inflammatory reaction of the nodular P. type. There are indications of one or various infections experienced once or repeatedly. Scarlet fever, angina, influenza, syphilis, gonorrhea, erysipelas, diphtheria, rheumatism, typhoid fever are indicated. Special attention is paid to syphilis as a disease that generally causes numerous forms of vascular changes. By 1927, 30 cases of nodular P. with syphilis in the history had accumulated, of which 25 had negative Wassermann reaction, 2 had positive only at the first examination and 3 had constantly positive; of 5 cases with positive Wassermann reaction, in 3 the syphilitic infection was recent, in 2—old. By the majority of authors, the syphilitic nature of nodular P. is rejected, although the leading role of syphilis in individual cases is not denied. Attempts to produce nodular P. experimentally gave very questionable results. Some significance in elucidating the role of infection in the etiology of nodular P. is had by findings of this disease in animals. The first of these were in the Hamburg zoo in a deer (Cervus axis). In recent years, 3 cases in a pig, 1—in a calf, 2—in a cow and 1—in a dog have been described. These observations once again emphasize the incorrectness of interpreting nodular P. as a syphilitic suffering in all cases. Thus, the view is increasingly established that any infection causing damage to the vascular wall can serve as an etiological factor for nodular P. The difference of nodular P. from those vascular changes that are usually observed in infections, some (Gruber) explain by the allergic (namely hyperergic) nature of inflammation in the first case, others—simply by its unusual extent and strength, depending on the particular vulnerability of the vascular system in this subject. Indeed, if in nodular P. microscopic examination is performed not only of the affected arteries but also of parts of the vascular apparatus that appear normal to the naked eye, then insignificant focal changes can often be found in them, which undoubtedly represent the initial stages or a milder manifestation of the same process, but at the same time differing in no way from the pictures described by a number of authors in arteries in the most diverse infectious diseases (scarlet fever, influenza, typhoid fever, diphtheria, erysipelas, sepsis, etc.). This connection between simple focal infectious arteritis and nodular P. finds confirmation, among other things, in the localization of the process, since in both cases the most affected organs are the heart and kidneys. In typical cases, the separation of nodular P. from other arteritis on morphological data is quite possible. In less typical cases, careful clinical-anatomical analysis is necessary. The difference from syphilitic arteritis consists of: 1) the predominant localization in syphilitic arteritis of vessels of the brain, more often its base and meninges, and the relatively rare localization of nodular P. in these places; 2) absence of spirochetes, gummas and giant cells in nodular P.; 3) absence or insignificant regeneration of elastic fibers in nodular P. and, conversely, its presence up to the formation of new membranes in syphilitic arteritis; 4) special involvement in the process in syphilitic arteritis of the intima, up to obliteration of the lumen or formation of multiple lumens; 5) rare development of aneurysms in syphilitic arteritis and frequent in nodular P. But these differences concern more syphilitic arteritis of the obliterative endarteritis type (variete obliterante of the French). Arteriitis syphilitica aneurysmatica (variete ectasiant of the French) with large destructions of the wall is morphologically in essence not different from nodular P. Local consequences of nodular P. (directly in the vessel and its wall)—thromboses and aneurysms (Gruber, 1917—from 44 cases, the first occurred 34 times and the second 29 times).

Thrombi are found exclusively at the site of changes in the wall, both mural and occlusive. In connection with the organization of the thrombus, sometimes a thickening of the intima, obliteration of the lumen, and vascularization develop. Thrombosis of large vessels can cause emboli. Aneurysms are usually multiple and more common in fresh foci; in scarred areas, tears and ruptures of the wall, hemorrhages into the wall and surrounding tissue, and into various cavities are noted. The multiple small hemorrhages in the brain and skin without involvement of their vessels in nodular P. are considered as a consequence of the same cause that led to nodular P. Transitions of the process to the wall of veins have been described—so-called periphlebitis. Among the focal changes in organs, local circulatory disorders are of great importance as the main consequence of nodular P. The most frequently affected organs are the kidneys, heart, liver, stomach, mesentery, skeletal muscles, spleen, sexual organs, skin, pancreas; rarely affected are the lungs, pleura, adrenal glands, vasa vasorum of the aorta. Often there is simultaneous involvement of several organs—kidneys, heart, liver—but there can also be exclusive involvement of one organ, for example, the kidneys or heart. Kidney involvement is most common (according to Gruber, in 80 out of 109 cases of nodular P., i.e., more than 75%); in connection with nodular P. of the kidneys, infarcts are most often encountered. Nodular P. of the heart was observed in 65% of cases, more often in the main trunks or large branches of the coronary arteries; the process can be easily determined macroscopically in the form of nodules under the epicardium; consequences are necroses and infarcts, scars of various sizes; widespread infiltrates between muscle fibers and diffuse growth of connective tissue have also been noted. In nodular P. of the liver (approximately in 60% of cases), the changes are similar; extensive necroses accompanied by jaundice, red infarcts have also been described; involvement of the gallbladder vessels occurs in 10%; in 1 case, exclusive involvement was described. Nodular P. of the gastrointestinal tract in almost half of all cases results in infarcts, necroses, ulcers, complications, perforating peritonitis, hemorrhages into the wall and into the intestinal cavity; hemorrhagic colitis has been described. Nodular P. has been described not only of the arteries of the intestinal wall, but also of the arteries of the mesentery and peritoneum (about 36%). Nodular P. of the pancreas is observed in 20% of all cases of nodular P. Involvement of peripheral nerves occurs (in 18% of cases), with severe degenerative changes in nerve fibers observed with minimal changes or their absence in the vascular wall and vice versa. Nodular P. of skeletal muscles has been described in 32 cases, with a discrepancy between changes in the muscles and their arteries, as in the nerves. Involvement of the spleen and adrenal glands was noted in 15 cases, of the skin and subcutaneous tissue in 14 cases, of the brain and meninges in 9 cases, and of other organs in 1-2 cases. Sternberg described isolated involvement of the medium and small branches of the pulmonary artery with obliteration of the vessels, aneurysms, ruptures, and infarction of the lower lobe of the left lung and fatal hemorrhage into the pleura.

M. Zakhaevskaya. Clinic of nodular P. Nodular P. is more frequently observed in men, predominantly at middle age (20-30 years), but cases have been described in early childhood and old age. The disease in most cases begins gradually, insidiously, mainly with general phenomena-weakness, elevated temperature, pain in the extremities. Subsequently, the clinical picture of the disease consists of general and local phenomena. General phenomena--both those just mentioned and those developing during the further course of the disease (anemia, exhaustion).- depend on the influence of the corresponding infectious agent on the entire organism. But they can also be a consequence of impaired function of individual organs as a result of predominant damage to their arteries. For example, the so frequent in nodular P. lesion of renal arteries and arterioles can give corresponding general phenomena through the developing renal insufficiency. The main cause of the extraordinary diversity of the clinical picture of nodular P. is the diversity in localization in general and in the predominant localization of vascular changes in various organs-in particular. Of the general phenomena, the most constant should be considered general weakness, general exhaustion and anemia («chlorotic marasmus» in the expression of Kussmaul and Meyer). Anemia has the character of the so-called secondary anemia and usually reaches only moderate degrees. To what extent it is a consequence of blood loss, to what extent of suppression of the blood-forming function of the bone marrow-sometimes it is difficult to decide. Leukocytosis, as a rule neutrophilic, sometimes reaches a significant degree, but in general neither the total number of leukocytes nor the leukocyte formula represents anything characteristic for nodular P. Elevated temperature is not obligatory, but is often observed either in the form of subfebrile temperature or in the form of irregular, atypical, often intensifying fever. The degree of temperature elevation as a rule corresponds to the intensity (pace) of the entire pathological process. New waves of febrile temperature usually accompany the so characteristic for nodular P. repeated exacerbation of the pathological process. Increased pulse is usually stronger than corresponds to the elevated temperature, and is apparently caused by the general toxic-infectious effect on the circulatory organs-on the cardiac muscle as well as on the vegetative cardiovascular centers. Blood pressure in nodular P. as a rule shows a tendency to decrease, but sometimes also gives an increase. The tendency to decrease depends on the lowering of arterial pressure effect of the exhausting infectious disease, and sometimes can also be from severe damage to the cardiac muscle with impaired patency of the coronary branches. The sometimes observed elevation of arterial pressure in nodular P. is a manifestation of the developing renal insufficiency, which sometimes results from intense damage to renal arterioles. In these latter cases, hypertension is sometimes accompanied by signs of left ventricular hypertrophy. Of other phenomena from the cardiovascular system in nodular P. should be noted: 1) frequently observed signs of cardiac or cardiovascular insufficiency and 2) pains in the heart area, occasionally of the type of angina pectoris. Various clinical symptoms from the kidneys in nodular P. are very frequent and belong to the most typical features of the clinical picture of nodular P. Hematuria is observed, sometimes in the absence of other renal symptoms, sometimes as one of the features of the picture of renal infarction, acute or subacute (hemorrhagic) glomerulonephritis. At the same time, phenomena of renal insufficiency and uremia may develop, from which patients often die. More rarely nodular P. is accompanied by clinical manifestations of nephrosis. These diffuse kidney lesions can be not only a consequence of the specific for nodular P. damage to blood vessels, but also a manifestation of the direct effect on the kidneys of the same toxic-infectious agent that causes the specific for nodular P. vascular changes. In the clinical picture of nodular P. there are almost always painful phenomena from the abdomen, mainly its upper part. Sometimes they accompany the disease from beginning to end, sometimes develop in the form of alarming signs of acute peritonitis, pancreatitis, renal colic with vomiting, collapse etc. These acute severe phenomena in nodular P. have repeatedly been the reason for surgical intervention as a result of various erroneous diagnoses. Often a picture of hemorrhagic colitis accompanied by severe colics is observed. In other cases a picture of internal hemorrhage develops acutely, ending in death. As signs of impaired liver function are noted jaundice, various manifestations of hepatic insufficiency, severe pains in the liver area and its tenderness and that of the gallbladder. In some cases, apparently in those where the process runs more acutely, enlargement of the spleen is observed, which should be considered as a manifestation of the general reaction of the organism and only in rare cases as a result of damage to the blood vessels of the spleen. Among the most characteristic features of nodular P. should be included phenomena from the peripheral nerves-drawing, tearing, shooting pains in the extremities, observed in almost all cases. Convulsive phenomena from muscles are not infrequent, later their atrophy and paresis. At the beginning areas of cutaneous hyperesthesia are observed, later of reduced sensitivity, decrease of tendon reflexes. If all these phenomena are sharply expressed, the picture of the disease resembles polyneuritis or polymyositis. It should be noted that histological changes from the peripheral nerves are observed significantly less frequently than clinical ones. Obviously part of these phenomena from the nervous system should also be considered as a manifestation of the direct influence of the pathogenic agent on the nervous system. Phenomena from the central nervous system occur much less frequently. Phenomena of encephalomalacia and cerebral hemorrhage have been described. Changes from the skin and subcutaneous tissue in the sense of development in them of nodules of P. are comparatively rare (not more often than in 15% of cases), but occupy a special position, because only they make it possible to easily and confidently make a diagnosis of nodular P. during life, if not on the basis of combination of nodules in the skin with other more characteristic manifestations of nodular P., then at least on the basis of histological examination of the excised nodule. These nodules are the size from poppy to millet seed, at first they are soft; once having appeared, they either quickly disappear (in 48, even 24 hours), or harden and remain for many weeks and even months. Besides these nodules from the skin (in approximately 7% of cases) hemorrhages are observed---petechial or in the form of small spots. The Rumpel-Leede symptom (otherwise the endothelium symptom of Stefan) is even in those cases where there are no spontaneous skin hemorrhages, as a rule distinctly expressed. From the upper respiratory tract, lungs, sexual organs, sense organs usually no symptoms are observed. Diagnosis. During life the diagnosis of nodular P. in most cases has not been made to this day and if made, then almost exclusively in those cases where the skin nodules suggested the idea of nodular P. If one could imagine the combination of the above-mentioned phenomena from 1) peripheral nerves, 2) kidneys and 3) abdominal cavity against the background of 4) «chlorotic marasmus», then it would seem that recognition of nodular P. is not so difficult. In reality however this diagnosis is not so simple, because the combination of these more characteristic symptoms is actually observed comparatively rarely-not more than in 20% of cases. In the case if one or two of these main manifestations of the disease are present, then the addition of other less common manifestations diverts the thought toward other diagnostic assumptions. In general the polymorphism of the clinical picture in the sense of great diversity of combinations of symptoms from various organs and systems-is a feature of nodular P., which most of all hinders the diagnosis. And in nodular P., as in all cases of recognition of rarer forms of diseases, the decisive importance for making the diagnosis is the emergence of the thought about the possibility of the presence of this form of disease. Trichinosis, polyneuritis, polymyositis and subacute sepsis- are those diseases that most often give a clinical picture similar to nodular P. In those cases of nodular P. where manifestations of this or that localization of arterial damage predominate, corresponding differential diagnostic difficulties may arise: with predominant damage to arteries or arterioles of the kidneys nodular P. resembles acute hemorrhagic nephritis; with damage to mesenteric and intestinal arteries-resembles hemorrhagic colitis or peritonitis etc. The course of the disease-in the sense of more or less acute or subacute character-is very diverse, duration on average about 2 months, varying from a few days to many months. Characteristic is the wave-like or remitting course, and simultaneously the general phenomena (fever, cachexia etc.) and this or that local phenomena weaken or intensify.

Death rarely occurs from general exhaustion, much more often from severe consequences of local lesions of larger arteries—from hemorrhage, perforations, peritonitis due to necrosis of an intestinal loop, or from uremia as a result of kidney lesions.—Prognosis. The overall mortality from nodular P. is approximately 90%; in each individual case, the prognosis depends on the nature of the course of the process and on the presence and intensity of various local lesions.—Treatment of nodular P. is not specific. It must for now be purely symptomatic. Speaking of special prevention of nodular P. is also not yet appropriate, since the etiology and pathogenesis of nodular P. have not yet been sufficiently clarified, Dr. Lang.