Chapter 054. Skin Manifestations of Internal Disease (Part 12)

In the diffuse forms of hyperpigmentation, the darkening of the skin may be of equal intensity over the entire body or may be accentuated in sun-exposed areas. The causes of diffuse hyperpigmentation can be divided into four major groups—endocrine, metabolic, autoimmune, and drugs. The endocrinopathies that frequently have associated hyperpigmentation include Addisons disease, Nelson syndrome, and ectopic ACTH syndrome. In these diseases, the increased pigmentation is diffuse but is accentuated in the palmar creases, sites of friction, scars, and the oral mucosa. An overproduction of the pituitary hormones α-MSH (melanocyte-stimulating hormone) and ACTH can lead to an increase in...
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Chapter 054. Skin Manifestations of Internal Disease (Part 12) Chapter 054. Skin Manifestations of Internal Disease (Part 12) In the diffuse forms of hyperpigmentation, the darkening of the skin may beof equal intensity over the entire body or may be accentuated in sun-exposedareas. The causes of diffuse hyperpigmentation can be divided into four majorgroups—endocrine, metabolic, autoimmune, and drugs. The endocrinopathies thatfrequently have associated hyperpigmentation include Addisons disease, Nelsonsyndrome, and ectopic ACTH syndrome. In these diseases, the increasedpigmentation is diffuse but is accentuated in the palmar creases, sites of friction,scars, and the oral mucosa. An overproduction of the pituitary hormones α-MSH(melanocyte-stimulating hormone) and ACTH can lead to an increase inmelanocyte activity. These peptides are products of the proopiomelanocortin geneand exhibit homology; e.g., α-MSH and ACTH share 13 amino acids. A minorityof the patients with Cushings disease or hyperthyroidism have generalizedhyperpigmentation. The metabolic causes of hyperpigmentation include porphyria cutaneatarda (PCT), hemochromatosis, vitamin B12deficiency, folic acid deficiency,pellagra, malabsorption, and Whipples disease. In patients with PCT (seeVesicles/Bullae, below), the skin darkening is seen in sun-exposed areas and is areflection of the photoreactive properties of porphyrins. The increased level of ironin the skin of patients with hemochromatosis stimulates melanin pigmentproduction and leads to the classic bronze color. Patients with pellagra have abrown discoloration of the skin, especially in sun-exposed areas, as a result ofnicotinic acid (niacin) deficiency. In the areas of increased pigmentation, there is athin varnish-like scale. These changes are also seen in patients who are vitamin B6deficient, have functioning carcinoid tumors (increased consumption of niacin), ortake isoniazid. Approximately 50% of the patients with Whipples disease have anassociated generalized hyperpigmentation in association with diarrhea, weightloss, arthritis, and lymphadenopathy. A diffuse slate-blue color is seen in patientswith melanosis secondary to metastatic melanoma. Although there is a debate as towhether the color is due to single-cell metastases in the dermis or to a widespreaddeposition of melanin resulting from the high concentration of circulating melaninprecursors, there is more evidence to support the latter. Of the autoimmune diseases associated with diffuse hyperpigmentation,biliary cirrhosis and scleroderma are the most common, and occasionally bothdisorders are seen in the same patient. The skin is dark brown in color, especiallyin sun-exposed areas. In biliary cirrhosis the hyperpigmentation is accompanied bypruritus, jaundice, and xanthomas, whereas in scleroderma it is accompanied bysclerosis of the extremities, face, and, less commonly, the trunk. Additional cluesto the diagnosis of scleroderma are telangiectasias, calcinosis cutis, Raynaudsphenomenon, and distal ulcerations (see Telangiectasias, above). The differentialdiagnosis of cutaneous sclerosis with hyperpigmentation includes the POEMS[polyneuropathy; organomegaly (liver, spleen, lymph nodes); endocrinopathies(impotence, gynecomastia); M-protein; and skin changes] syndrome. The skinchanges include hyperpigmentation, skin thickening, hypertrichosis, andangiomas. Diffuse hyperpigmentation that is due to drugs or metals can result fromone of several mechanisms—induction of melanin pigment formation, complexingof the drug or its metabolites to melanin, and deposits of the drug in the dermis.Busulfan, cyclophosphamide, 5-fluorouracil, and inorganic arsenic induce pigmentproduction. Complexes containing melanin or hemosiderin plus the drug or itsmetabolites are seen in patients receiving chlorpromazine and minocycline. Thesun-exposed skin as well as the conjunctivae of patients on long-term, high-dosechlorpromazine can become blue-gray in color. Patients taking minocycline maydevelop a diffuse blue-gray, muddy appearance in sun-exposed areas in addition topigmentation of the mucous membranes, teeth, nails, bones, and thyroid.Administration of amiodarone can result in both a phototoxic eruption(exaggerated sunburn) and/or a brown or blue-gray discoloration of sun-exposedskin. Biopsy specimens of the latter show yellow-brown granules in dermalmacrophages, which represent intralysosomal accumulations of lipids,amiodarone, and its metabolites. Actual deposits of a particular drug or metal inthe skin are seen with silver (argyria), where the skin appears blue-gray in color;gold (chrysiasis), where the skin has a brown to blue-gray color; and clofazimine,where the skin appears ...