Erythropoietic uroporphyria associated with myeloid malignancy

Erythropoietic uroporphyria associated with myeloid malignancy is a rare acquired form of porphyria that occurs in the context of myelodysplastic syndromes (MDS) or other myeloid neoplasms. Unlike the inherited forms of porphyria, this condition arises due to somatic mutations in the UROS (uroporphyrinogen III synthase) gene within the clonal hematopoietic cells of the bone marrow. The defective enzyme leads to massive accumulation of uroporphyrin I and coproporphyrin I in red blood cells, plasma, and skin, producing a clinical picture that closely resembles congenital erythropoietic porphyria (CEP, Günther disease) but with adult onset. The condition primarily affects the skin and the hematopoietic system. Patients typically develop severe cutaneous photosensitivity with blistering, skin fragility, erosions, and scarring on sun-exposed areas. Hypertrichosis, hyperpigmentation, and red-brown discoloration of the teeth (erythrodontia) may also occur. Red or dark urine due to excess porphyrin excretion is common. Hemolytic anemia and splenomegaly can develop as a consequence of porphyrin accumulation in erythrocytes. Because the underlying cause is a myeloid malignancy, patients also face the complications associated with their hematologic disease, including cytopenias and potential progression to acute myeloid leukemia. Treatment is challenging and must address both the porphyria and the underlying myeloid malignancy. Sun avoidance and photoprotection are essential to minimize skin damage. Management of the hematologic malignancy may include supportive care, hypomethylating agents, or allogeneic hematopoietic stem cell transplantation, which can potentially cure both the malignancy and the porphyria by replacing the abnormal clonal cells. Red blood cell transfusions may help suppress erythropoiesis and reduce porphyrin production. The prognosis depends largely on the course of the underlying myeloid neoplasm.

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