Mikulicz Disease

MIKULICZ DISEASE (Mikulicz), a distinctive symmetrical swelling of the salivary and lacrimal glands. Attention was first drawn to this condition by Fuchs (Fuchs; 1891), and it was thoroughly studied by Mikulicz. For this reason, some researchers consider it more accurate to speak of Fuchs-Mikulicz disease. According to Mikulich's own description and subsequent researchers, Mikulicz disease is classified as a rare disease; it affects people of different ages, but predominantly middle-aged individuals who were previously healthy; no preference for either sex is noted. The underlying swelling of the salivary and lacrimal glands begins imperceptibly, insidiously, and progresses very slowly, over months and years. Most frequently, both lacrimal glands and the three pairs of major salivary glands (parotid, submandibular, sublingual) are symmetrically affected; at the same time, there are cases where, in addition to the aforementioned glands, the Nuhnian glands and small salivary glands of the pharynx, throat, gums, lips, and larynx become swollen. On the other hand, sometimes only the pair of lacrimal glands, or only the salivary glands, or finally only one pair of the latter (most often the parotid) are affected. As a rule, the symmetric glands on both sides become diseased simultaneously; much less frequently does the process begin earlier on one side and then appear on the other. The slowly and uniformly developing swelling of the glands does not distort their configuration, does not violate the capsule; the glands remain completely mobile. The consistency of the glands becomes somewhat denser than normal. In most cases, the swollen glands are completely painless and only occasionally somewhat sensitive to pressure. With significant development of the swelling, the contours of the face change, and disturbances in chewing, speech may occur, and as a result of swelling of the laryngeal glands, difficulty in breathing. One of the most unpleasant symptoms is dryness of the mouth and the conjunctiva of the eyes, which is observed in the late stages of the disease and is associated with a decrease or cessation of the secretory function of the affected glands. The course of Mikulicz disease can be very different; sometimes the swelling of the glands continuously progresses slowly; in other cases, after starting, it stops for a long time or even undergoes regression, and after some time returns again; cases of spontaneous permanent recovery are also observed. Death can occur only from concomitant diseases. The above description refers to so-called classical cases of Mikulicz disease, in which the disease is limited to the lacrimal and salivary glands, affected in one combination or another. However, in addition to these cases, there are also cases where, along with the swelling of the lacrimal and salivary glands, there is a universal increase in lymph glands and the spleen; these latter cases, in which the changes in the lacrimal and salivary glands play the role of as it were one component of some general systemic disease, greatly helped to clarify the essence of Mikulicz disease (see below). Pathological-anatomical study of the lacrimal and salivary glands in Mikulicz disease established that in some cases the swelling of the glands is associated with the proliferation of typical lymphoid tissue in these glands, whereas in other cases it is a matter of proliferation of granulation tissue in the glands, similar to that which is typical for lymphogranulomatosis (see). On this basis, Heineke proposed to distinguish two types of Mikulicz disease: 1) symmetrical lymphomatosis and 2) symmetrical granulomatosis of the salivary and lacrimal glands; many authors retain this division to the present time. 1. In Mikulicz disease of the lymphomatous type, the salivary and lacrimal glands are enlarged, but retain their characteristic configuration; on the surface of the section in cases of fresh lesions, the lobular pattern is preserved, the lobules are only increased in volume, whereas in the late stages the lobular pattern is erased and the tissue acquires a homogeneous, fatty, gray-pink appearance. Microscopic research reveals that the basis of the gland changes is the proliferation of lymphoid tissue from small lymphocytes, which as a rule originates from those places where in normal salivary and lacrimal glands lymph follicles and often small lymph glands are located, i.e., from the gates of the lobules and the vicinity of larger ducts and vessels; from here the lymphoid proliferation penetrates into the lobules and gradually disconnects and destroys the glandular parenchyma cells. The interlobular connective tissue spaces, which remain untouched at first, are later also infiltrated by lymphoid tissue; also the capsule of the glands. Sometimes among the lymphoid elements an admixture of eosinophils is noticeable; in some cases the formation of true follicles with light centers in the proliferated lymphoid tissue has been described. Proliferation and desquamation of the epithelium of the excretory ducts, the formation of multinucleated cells from glandular epithelium are described. In the late stages, sclerosis of the proliferated lymphoid tissue often occurs. 2. Mikulicz disease of the granulomatous type is characterized by the same change in the appearance of the lacrimal and salivary glands; however, here the lesion does not proceed so uniformly throughout the gland tissue, and the erasure of the pattern on the surface of the gland section occurs earlier. Clinically, the glands appear dense and somewhat painful on pressure, which are considered signs distinguishing this type of Mikulicz disease from the lymphomatous type. Histological research reveals that here there is intralobular proliferation of granulation tissue consisting of epithelioid and lymphoid cells, eosinophils, plasma cells, and typical Sternberg giant cells, in other words-tissue characteristic in structure for lymphogranulomatosis. As the study of the initial periods of this type of Mikulicz disease shows, the proliferation of granulation tissue also begins in the areas of normal location of lymphatic follicles and glands in the salivary and lacrimal glands, i.e., at the gates of the lobules, and from these areas spreads into the lobules, destroying their parenchyma; interlobular connective tissue and capsule are affected later. A nodular arrangement of the granuloma or even the formation of epithelioid tubercles with typical Langhans giant cells is often noticed. In the late stages of the disease, sclerosis of the granulation tissue is usually observed, and with it a decrease and densification of the affected glands. As for those already mentioned cases above, in which along with the swelling of the salivary and lacrimal glands there is an increase in lymph glands and the spleen, pathology has established that they too are of two categories. 1. In one part of such cases, in the lymph glands, spleen and generally in the lymphadenoic tissue, the picture of hyperplasia characteristic of systemic lymphadenoses is found; at the same time in the salivary and lacrimal glands there is a picture of lymphomatosis. In most such cases, the blood is unchanged, in some it presents a picture of lymphatic leukemia. From this it becomes clear that these cases belong to lymphatic leukemia or (more rarely) leukemia, and the change in the salivary and lacrimal glands, where in essence it is a matter of change not of the proper gland tissue, but of the lymphadenoic tissue contained in these glands, represents a partial manifestation of the general aleukemic (more rarely leukemic) lymphadenosis or lymphomatosis. 2. In other cases, in the lymph glands and in the spleen there were changes characteristic of lymphogranulomatosis and at the same time granulomatous changes in the salivary and lacrimal glands. Obviously, these cases represent cases of general lymphogranulomatosis with the participation of the lymphadenoic tissue contained in the salivary and lacrimal glands in the process. The solution of the question of the essence of Mikulicz disease at the present time does not present difficulties. Pathological-anatomical study of so-called classical cases of Mikulicz disease and those in which Mikulicz disease is combined with a general lesion of the lymphadenoic tissue of the body clarified two circumstances: 1) the basis of Mikulicz disease is the change not of the proper tissue of the salivary and lacrimal glands, but of the lymphadenoic tissue contained in these glands. 2) The change in the lymphadenoic tissue of the salivary and lacrimal glands, giving the symptom complex of Mikulicz disease, is in its essence extremely different. From these two positions it follows that Mikulicz disease does not represent a disease in the sense of a definite nosological unit, as Mikulich initially thought, who even assumed a special infectious etiology of the disease he described, but is purely an external expression of various lesions of the lymphadenoic tissue that makes up the salivary and lacrimal glands. Most often it is lymphomatosis or aleukemic hyperplasia of the lymphadenoic tissue of the salivary and lacrimal glands, and if the change is limited only to the salivary and lacrimal glands, such cases should be considered as a special local aleukemic lymphadenosis, local aleukemic lymphoma; if lymph glands and spleen are involved at the same time, then the symptom complex of Mikulicz disease is only a partial expression of general aleukemic (more rarely leukemic) lymphadenosis. It can be added that general aleukemic and leukemic myelosis can also be accompanied by the involvement of the salivary and lacrimal glands and a clinical picture of Mikulicz disease.

In second place in frequency as the basis of M. b. lies lymphogranulomatosis, which affects the lymphadenoid tissue of the salivary and lacrimal glands either in isolation or together with general involvement of the lymph glands and spleen. Lymphomatosis and lymphogranulomatosis, however, do not exhaust the diseases that can give a picture of M. b. One can confidently think that some of the granulomatous forms of M. b., which Lang cites, belong to tuberculous involvement of the lymphadenoid tissue of the salivary and lacrimal glands; in some of these cases, tuberculous bacilli were found in the granulomas; often there was simultaneously tuberculous involvement of the lungs or lymph glands. Nagel attributes some cases of M. b. to a manifestation of status lymphaticus. He, as well as Küttner, describe syphilitic forms of M. b. A transient symptom-complex of M. b. has also been observed in gonorrhea. There are observations that some cases presenting a picture of M. b. turned out to be symmetrical lymphangiomas of the salivary glands. Finally, lymphosarcomatosis can begin in the lymphadenoid tissue of the symmetrical salivary and lacrimal glands, initially giving a picture of M. b. All this taken together emphasizes that M. b. is merely a symptom-complex, in the basis of which can lie diseases that are different in essence.