 A more severe skin manifestation, pyoderma gangrenosum, is characterized painful pustules or nodules that become ulcers which progressively grow.UC increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism (blood clots in the lungs).The immune system may attack the red blood cells, leading to autoimmune hemolytic anemia.