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a Sign of Systemic Disease-skin Disorders

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Increased pigmentation of the skin is seen in a number of systemic diseases. In porphyria cutanea tarda, hyperpigmentation occurs on the face and arms, presumably because of the photosensitizing effect of porphyrins. It is accompanied by hirsutism of the face together with skin fragility or blistering of the dorsal hands. There often is laboratory evidence of liver disease. Elevated urine levels of uroporphyrin and coproporphyrin are diagnostic. When skin lesions suggestive of porphyria cutanea tarda are accompanied by gastrointestinal symptoms, neurologic problems, or psychiatric changes, stool porphyrins should be obtained to evaluate for the possible presence of variegate porphyria.

In Addison’s disease, hyperpigmentation occurs over the entire body, but there is accentuation of the brown color in old scars and in skin creases. The nail beds and the oral mucosa may also become hyperpigmented. Hyperpigmentationin Addison’s disease is due to increased output of pituitary hormones such as melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH), both of which are capable of stimulating pigment production. Low semm cortisol levels are present, and the diagnosis is established by the failure of cortisol levels to rise following appropriate adrenal stimulation. In patients whose Addison’s disease occurs as part of a multiglandular deficiency syndrome, vitiligo may also be present.

In scleroderma, hyperpigmentation is generalized, but there is accentuation of the brown color on the dorsal surface of the arms and hands. Occasionally, vitiligo-like mantles of hypopigmentation will be interspersed within areas of darkened skin. The mechanism for the pigmentation is unknown. Diagnosis is supported by the concomitant presence of Raynaud’s phenomenon, sclerodactyly, decreased esophageal motility, and, in advanced cases, pulmonary, cardiac, and renal disease. Skin biopsy, to determine the degree of sclerosis, helps to confirm a clinical diagnosis.

The generalized hyperpigmentation of hemochromatosis is more slate colored or bronze than brown. Jaundice may also be present. The mucous membranes become hyperpigmented in 20% of patients. The pathogenesis of the pigmentation is unknown. Glucose abnormalities are present, and the diagnosis is confirmed by liver biopsy, which on appropriate staining demonstrates elevated levels of hepatic iron.

Hyperpigmentation associated with malignants is most classically found with carcinoma of the lung. The pigmentation occurs because of the MSH-like activity of polypeptides elaborated by such tumors. Generalized melanosis may also be seen with advanced, widespread melanoma, in which case the color is due to the direct production of pigmented compounds by the malignant cells.

The pigmentation in acanthosis nigricans, although generalized, is most notable in intertriginous areas where it is accompanied by the presence of densely pigmented, soft velvety ridges. These changes are particularly accentuated on the side of the neck, in the axillae, and in the groin. Increased pigmentation of mucosal surfaces is also often present. The mechanism responsible for the pigmentation is unknown, but increased MSH output is suspected. Acanthosis nigricans is most commonly found as an unimportant aspect of obesity, but its occurrence in children and adults of normal weight should raise a question of associated malignancy. Central nervous system tumors are most often the cause of acanthosis nigricans in children, whereas gastrointestinal tumors are usually found in adults with this condition.

Most patients with severe neurofibromatosis show some evidence of generalized hyperpigmentation in addition to the presence of cafe-au-lait patches .

Diffuse hyperpigmentation sometimes occurs as a result of chemotherapeutic agents administered to patients with varying types of malignancy. In such situations, pigmented bands on the nails may also be noted.

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