Siderophilic melanoderma due to iron overload

Specialty: Hematology.

• Tanned diabetes
• hyperpigmentation due to hemosiderosis
• hematological tanned skin

Why it occurs

• Hereditary hemochromatosis type 1 (homozygous C282Y mutation in the HFE gene that causes uncontrolled intestinal iron absorption due to hepcidin deficiency, accumulating the metal in hepatocytes, pancreas and the basal cells of the epidermis, stimulating the synthesis of melanin)
• Secondary transfusional hemosiderosis (massive accumulation of iron in patients with chronic refractory anemias who receive repeated transfusion support, such as in Beta-Thalassemia major, Myelodysplastic Syndromes or Aplastic Anemia, as the human body lacks an active physiological pathway for iron excretion)
• Severe ineffective erythropoiesis (as in congenital or acquired sideroblastic anemias, where blocked medullary erythroid hyperplasia mechanically stimulates digestive iron absorption)
• Chronic alcoholic liver disease with secondary iron overload
• Porphyria cutanea Tarda (uroporphrinogen decarboxylase deficiency, closely linked to hepatic iron overload).

Initial workup

Quantitative determination of serum ferritin (values ​​typically greater than 1,000 ng/mL suggest high risk of irreversible organ damage) and percentage of transferrin saturation (typically >45%, and frequently >60-80% in advanced cases); molecular genetic analysis for common HFE gene mutations (C282Y, H63D, S65C); magnetic resonance imaging with T2* technique (T2* hepatic and cardiac MRI, non-invasive gold standard to quantify tissue iron concentration in milligrams per gram of dry tissue); liver biopsy for direct quantification of iron and evaluation of fibrosis or cirrhosis; fasting blood glucose, glycosylated hemoglobin (HbA1c) and pituitary hormonal profile (to rule out concomitant hypogonadotropic hypogonadism due to iron deposition in the anterior pituitary).

Standard management

• Deferasirox — iron chelator administered orally once a day; It binds to free iron and promotes its excretion through the fecal route, indicated in chronic transfusional iron overload or in patients with hemochromatosis not subject to phlebotomy.
• Deferoxamine — classic iron chelator administered by long-term continuous subcutaneous or intravenous infusion, reserved for severe iron overload with active cardiac involvement
• Deferiprone — oral iron chelator with excellent penetration capacity into cardiac tissue, usually used in combination with deferoxamine in severe thalassemias
• Therapeutic phlebotomy (physical procedure of periodically removing 400-500 mL of whole blood; first choice in non-anemic hereditary hemochromatosis to actively deplete body iron reserves).