Melanosis

MELANOSIS (melanosis), or melanopathia (melanopathia), is a pathological condition of the organism in which the pigment melanin accumulates in excessive amounts in places where it is normally found, i.e., in the skin—making the latter acquire all shades of brown or smokey-gray colors—as well as appearing where it is normally never encountered (in mucous membranes and internal organs). Melanosis of the skin is also called melanoderma (melanoderma) and can be congenital or acquired (the term "nigrism" essentially denotes the same thing). Melanosis may spread evenly over all body integuments or occupy only limited areas of it. If the process covers the entire body, it is noted that uncovered areas of the skin (head, hands), then such places which are already usually pigmented more strongly (breast nipple, genitalia, armpit, etc.), and finally such areas which are subject to stronger mechanical influences (skin folds and constrictions, linea alba), are pigmented more intensely than the rest of the body integuments. Diffuse melanosis of the skin integuments is observed in cases of internal secretion disorders, diseases of the genital organs, hemochromatosis, pernicious anemia, conditions leading to marasmus and cachexia, in old age; in certain intoxications (arsenic, salvarsan), in certain cases in occupationally hazardous industries (see below), and under intense irradiation with light rich in ultraviolet rays. Limited melanosis of the skin is encountered around chronic inflammatory foci or at the site of past inflammatory processes, during pregnancy, in the menopausal period, and in pediculosis. In addition, focal melanosis (congenital) is encountered in the form of freckles and birthmarks. In cases of diffuse melanosis of the skin, all integuments darken, acquiring a yellow-brown, smokey-gray, or bronze hue. The coloration depends, on the one hand, on an increase in the amount of pigment in the epidermis, and on the other hand, on the accumulation of melanin in the chromatophores of the corium. The appearance of diffuse melanoderma in connection with certain diseases of internal secretion organs stands out especially brightly (sometimes in combination with melanosis of the oral mucosa) in lesions of the adrenal glands (see Addison's disease). The essence of the relationship between pigment metabolism and the adrenal glands has not yet been definitively clarified; it is hypothesized that the failure of adrenal function causes the accumulation of tyrosine and dioxyphenylalanine in the skin, which are processed into melanin by the skin epithelium. Certain authors also hypothesize an increase in the tyrosine content in the skin in this regard. Melanosis of the skin is also observed in Basedow's disease and tetany; however, it is unknown whether melanosis arises as a result of the direct action of the respective affected glands or is caused by a simultaneously existing impairment of the function of the adrenal glands or sex glands. It is well known that an alteration or disorder of the function of the latter (female diseases, climacteric, pregnancy) can entail the occurrence of melanoderma, especially pregnancy, during which diffuse skin melanosis or (more frequently) limited pigmentations on exposed parts of the body can occur. On the face, they are designated as chloasma uterinum and represent gray or brownish spots on the nose, forehead, chin, upper lip, and eyelids. Melanoderma has also been described in pubertas praecox. The diffuse smokey-gray or bronze coloration of the skin integuments in hemochromatosis is also based on the accumulation of melanin in the basal layer of the epidermis and in the cells of the skin proper. It should, however, be remembered that in this disease, another pigment (hemosiderin) also accumulates in the thickness of the skin and its appendages. The dependence of enhanced skin pigmentation on diseases accompanied by general cachexia, anemia, and marasmus (tuberculosis, chronic syphilis, malaria, malignant neoplasms), as well as melanoderma appearing in old age, is still completely unclear. Skin changes in this case may be further aggravated by hyperkeratosis and hypertrophy of the papillae, due to which the picture of acanthosis nigricans arises: the skin thickens, darkens, and becomes similar to shagreen. It is possible that some "toxic" influences or enhanced protein breakdown, which as is known has significance for the formation of melanin, lie at the root of these changes. Finally, the mechanism of development of limited skin pigmentations arising in the vicinity or at the site of specific and nonspecific chronic inflammations is also little known. Pigmentation along the periphery of syphilitic papules is well known; the accumulation of melanotic pigment around inflammatory infiltrates in condylomas; the increase of pigment at the site of tubercular skin lesions, and many others. The so-called urticaria pigmentosa—a disease beginning in early childhood and distinguished by a large accumulation of melanin in the basal layer of the affected areas—should also be referred here. Limited melanosis of the skin also arises at the site of scratch marks in pediculosis; furthermore, on the basis of past hemorrhages and ulcerations, especially in the case of varicose veins of the leg (ulcus cruris) and as a result of insect bites. In hemorrhage, hemosiderin always participates in the pigmentation, which, however, never is deposited in the skin epithelium, but always only in the corium. Unna connects the appearance of melanosis in the neighborhood of skin hemorrhages with the local breakdown of erythrocytes, i.e., with the release of protein substances from blood hemoglobin, which are perceived by epithelial cells and processed by them into melanin. Therefore, the melanin formed during hemorrhage is called hemomelanin by Unna and is contrasted by him with ordinary "epithelial" melanin. Melanosis of the large intestine stands somewhat apart among other limited melanoses (see Intestine). Investigations by Pick and Brahn established that the pigment in intestinal melanosis is true melanin, formed here under the influence of oxidizing enzymes from aromatic protein complexes (tyrosine, phenylalanine, etc.) abounding in the large intestine during the splitting of the protein molecule and absorbed by the mucosa. It has been noted that chronic constrictions or tuberculous processes in the intestine leading to its narrowing aggravate the phenomenon of hyperpigmentation and that the presence of pigment can be detected microscopically much more often than macroscopically. Thus, the etiology of the described acquired melanotic hyperpigmentations is still far from clear and apparently is not uniform, just as the melanin itself found in one case or another is not uniform. Presumably, it must be considered that at the base of these hyperpigmentations lies an increased supply to the tissues producing melanin of the material from which the latter is formed, i.e., protein substances. Such material can enter the cell in excessive quantities from the outside (during inflammatory processes) or be formed within it itself through enhanced dissimilation (in toxic, cachectic, and other states). The process of pigment formation itself concludes with the accumulation in tissues of corresponding oxidizing enzymes and with the participation in some cases of light. The state of affairs is apparently somewhat different in the emergence of certain occupational melanodermas. Occupational melanoses developing as a result of the action of light on skin sensitized by photodynamic substances of the acridine and anthracene series (during work with coal tar, resins, lubricating oils, petroleum, etc.) are clinically characterized by the presence against a general dirty-brown background of a large number of comedo-like black plugs blocking the follicles, partly turning into folliculitis and acne in the future; in larger elements of the lesion, the formation of pustules is observed. Along with this, there are psoriasis-like and wart-like (Ehrmann) eruptions. Most frequently and sharply, these changes are expressed on the extensor surfaces of the forearms, on the back of the hands and the basic phalanges of the fingers; they are frequently observed on the neck, thighs, and trunk. Frequently at the same time, there is hyperpigmentation of the skin of the face and neck, which is always preceded by inflammatory phenomena (mostly in spring and summer) in the form of edema and hyperemia accompanied by itching. When occupational hazards are removed, these changes slowly regress, leaving pigmentation and sometimes small follicular scars. The prophylaxis of these occupational melanodermas consists chiefly in supplying workers with work clothing, in the mechanization of production, in rational ventilation, and in the observance of personal hygiene rules (daily washing of the entire body). Essentially, the accumulation of melanin in the basal layer of the epidermis and cells of the skin proper also takes place here, while such hyperpigmentation occurs only on the exposed parts of the body exposed to the action of light.

In view of the fact that such a phenomenon ("tar skin", "tar melanosis") occurs not only upon direct contact of the respective substances with the skin, but also upon their penetration into the organism through the swallowing of dust particles and the inhalation of vapors, it can be assumed that in this case melanosis develops not so much as a result of the direct action of the aforementioned occupational factors on the skin, but rather as a result of an increase in the skin's photosensitivity; it is known that anthracene, acridine, phenanthrene, and many other substances contained in coal tar and pitch possess photosensitizing properties. Cases of photodermatosis have also been described in electric welders working under conditions of exposure to light rich in ultraviolet rays (electric arc at a current of 150 to 300 amperes). In view of the fact that in some of these cases porphyrinuria is simultaneously observed in patients, it is possible that these melanoses are also explained by the activation of the skin to light. On the other hand, in some electric welders, photodermatosis is observed without the presence of porphyrinuria. An example of congenital pigmentary anomalies can serve as freckles. To inherited melanoses, one can also refer the peculiar genotypic disease xeroderma pigmentosum, as well as the so-called Mongolian spots (see). To congenital hyperpigmentations, some also attribute the unilateral hetero-hyperchromia of the eye, called by them melanosis iridis. Apparently related to this is also melanosis of the eye (melanosis oculi), i.e., such a change in it, in which in various membranes and accessory parts (mucous membrane of the eyelids, cornea, iris, sclera, choroid, optic disc, etc.) an excess content of pigment is discovered, located either diffusely, due to which the affected parts acquire a slate-bluish, brown, or even black color, or in the form of small or large spots. On the cornea (sometimes of both eyes), the spots can have the characteristic shape of a spindle elongated in the vertical direction ("Krukenberg spindle"). A certain developmental defect in the sense of hyperpigmentation is also represented by birthmarks. By themselves, they are an example of local restricted melanosis of the skin, whereas malignant melanomas originating from them can become a source of diffuse melanosis of both the skin and the bone marrow and all internal organs (according to literature data, only the central nervous system remains unaffected, but according to the observations of E. Hertzenberg, the accumulation of pigment in glial elements and diffuse impregnation of capillary walls with melanotic pigment are also possible in the brain). In this case, both the skin and all organs, especially the liver, spleen, kidneys, and lungs, as well as the bone marrow, turn out to be colored in a smoky-gray, and sometimes even in a completely black color; this depends on the fact that melanin accumulates in large amounts in connective tissue cells, vascular endothelium, reticuloendothelium, and certain epithelial elements (of the kidneys, lungs). It is believed that it is released upon the breakdown of the melanotic tumor and its metastases and, in a dissolved, partly reduced (colorless) state in the form of melanogen, floods the circulatory system, leading to melanemia. (Transudate and urine can also be colored - see Melanuria.) From the blood and other fluids, melanogen is absorbed by the aforementioned cellular elements, is oxidized into melanin, which, accumulating in the form of grains and clumps, imparts a characteristic color to the corresponding organs and skin. Despite the fact that the previously described diffuse skin melanosis and that skin and internal organ melanosis observed in malignant melanomas have the same morphological picture, they are essentially profoundly different processes: in the first case, hyperpigmentation occurs due to an increase in melanin autochthonously produced by the cell itself, whereas in the second case, hyperpigmentation is merely a consequence of the fact that cells absorb the pigment or pigment precursor (melanogen) formed in another place and brought by the bloodstream.

E. Hertzenberg. Melanosis corii degenerativa of Siemens is a rare pigmentary anomaly of the skin, first described by Sulzberger (1928) under the name "incontinentia pigmenti"; it begins at an early age or exists from birth; clinically it is characterized by spotty, reticular, irregularly band-like, star- and spider-like pigmentations of a peculiar grayish-steel or dirty chocolate-brown color, sometimes with a livid-bluish tint, arising on the skin of the trunk, head, and extremities. After a more or less prolonged existence, the pigmentations spontaneously regress, sometimes leaving partial atrophy. Histologically, in the upper parts of the skin proper, mainly in the papillary and subpapillary layers, an abundant accumulation of pigment is found; connective tissue cells filled with pigment lie so densely at the very dermo-epidermal junction that the impression of their "contact" with basal cells is obtained. The latter are swollen, stain poorly, their nuclei are deformed, and they either do not contain pigment at all or have it only in a small amount. One can think of a functional anomaly of the basal cells, which, due to pathological permeability of the cell membrane for melanin, give off all or almost all of the melanin produced by them into the dermis ("pigment incontinence" according to Sulzberger). Naegeli observed familial melanosis corii degenerativa in a father and two daughters. Against recognizing melanosis corii degenerativa as a nevus is the regression of pigmentation, which is always observed as a rule. Riehl's melanosis is a peculiar skin disease, first noted at the end of the World War (1917) in Germany by Riehl. Clinically, Riehl's melanosis is characterized by the appearance without any visible cause of persistent spotty and diffuse pigmentations, mainly on exposed parts of the body. Riehl's melanosis begins with itching, after which in some cases minor hyperemia and peeling appear, while in the majority of cases, without any inflammatory phenomena, light and dark brown coloring of individual skin areas develops, sometimes with a bluish-gray tint. The cheeks, forehead, and lateral surfaces of the neck are usually affected most intensely; the process frequently involves the scalp and the dorsum of the fingers; sometimes covered parts of the body are affected, predominantly contacting surfaces (armpits, etc.). Pigment spots are more often associated with follicles, and follicular hyperkeratosis is frequently present simultaneously, especially pronounced on the dorsum of the fingers and on the scalp. Pigmentations exist for a very long time. Kerl, who observed 17 cases of Riehl's melanosis in the Vienna clinic, never saw a complete regression of pigmentation. The general condition is never disturbed. Both sexes are affected (somewhat more often women); occupation and age play no role. Histologically, a small round-cell infiltrate is found in the area of the superficial vascular network; above the infiltrate there are many pigment clumps; strong vascularization; edema of the papillae; in places loosening of the Malpighian layer; hyperkeratosis; in places horny plugs in the follicles. The main role in the occurrence of Riehl's melanosis is apparently played by some skin sensitizer with respect to light (photosensitizer). Riehl and his school look for this sensitizer in food products; according to Kerl, in Germany wartime bread (to which the majority of known cases of Riehl's melanosis fall) contained flour from leguminous plants, which in Riehl's opinion could play the role of such a photosensitizer (hence the name for Riehl's melanosis, "Kriegsmelanose", wartime melanosis). Habermann sees the sensitizer in an anthracene derivative - acridine, the vapors of which (in dust, etc.) sensitize the skin to the action of various irritants, including light. A number of authors join Habermann's view. Riehl's melanosis must be distinguished from a number of occupational melanodermas (tar and pitch melanoses; see above) associated with the external action of various lubricating oils, tar, coal, pitch, crude petrolatum, etc., as well as from melanodermitis toxica lichenoides (et bullosa) of Hoffmann (E. Hoffmann), in which follicular hyperkeratosis and acne-like folliculitis come to the fore, mainly on the extensor surfaces of the forearms, hands, and fingers, and which depends rather also on the local action of harmful products (Darier). In Riehl's melanosis, there is never a preceding acute inflammatory stage of pigmentation, which is almost always expressed in cases of occupational melanodermas (in so-called Schmieroldermatitis, Vaselindermatitis, etc.). In Riehl's melanosis, the participation of the endocrine apparatus is probable. Prophylaxis consists in protecting patients from the action of sunlight, since it worsens the course of the process. Treatment consists in the possible elimination of toxic products (being the putative sensitizer or containing it); locally, rubdowns with resorcinol or salicylic alcohol are recommended.