Methotrexate toxicity in the treatment of generalized pustular psoriasis

In a sixty-seven year old woman with a seventeen-year history of psoriasis, generalized pustular psoriasis of von Zumbusch developed. She was treated with parenteral methotrexate in two divided doses over a one-week period. Severe acute granulocytopenia developed with a drop in the white blood cell count from 27,000 to 400. We postulate that the pustular psoriasis stimulated rapid proliferation of the granulocyte series with a high percentage of the precursor cells in the bone marrow in the S-phase of the cell cycle. The subsequent dose of methotrexate resulted in a blockage of DNA synthesis in these cells and subsequent failure of maturation beyond the mitotic compartment in the bone marrow. Caution is recommended in the use of methotrexate in patients with acute generalized pustular psoriasis.