This literature marketed report as received from a healthcare professional refers to a 5 year old female patient with sickle cell hemoglobin C disease. On an unknown date the patient was vaccinated with PNEUMOVAX23 dose 2 in the right arm (dose, route and indication not reported). Other suspect therapies included meningococcal conjugate vaccine (unspecified) dose 2 in the left arm on the same date. In her previous clinic review, she reported leg pain that sometimes required pain medication and headache pain in the past 4 weeks. She also had chronic splenomegaly from her sickle cell disease. At this visit she received the PNEUMOVAX23 in her right arm and meningococcal conjugate vaccine in her left arm. The patient's immunization history included one dose of PNEUMOVAX23 two and a half years earlier, and a dose of the meningococcal conjugate 6 months prior to the event. She also had received four doses of th 7-valent conjugated pneumococcal vaccine, one dose of the 13-valent conjugated pneumococcal vaccine, the hepatitis B, and annual influenza vaccinations. Her mother had previously reported that she usually developed a low grade fever after receiving vaccinations, which she would treat at home with ibuprofen. The patient's past medical history included recurrent otitis media, requiring placement of tympanostomy tubes, and asthma, She also had a history of urticarial response to fire and bites, and skin-test confirmed allergies to dust, mold, mildew and cockroaches. In this report the patient experienced an unusual severe local reaction to PNEUMOVAX23. The patient presented with arm swelling, redness and pain as well as fever and nausea after immunization during a routine follow-up visit the day before. The patient developed pain in her head, neck and arm and a fever of 102.9 degrees F in the early morning the day after receiving the vaccine. Her mother administered ibuprofen. 10 h later, the mother reported a fever of 101.3 degrees F and right arm swelling with edema to the extent that it was difficult to put a shirt sleeve over the arm. The patient was brought to the Hematology clinic where she received ketorolac for pain and ondansetron for nausea reported at the clinic. Upon examination, it was noted that the right arm was tender with redness over the lateral aspect and swelling down to the elbow. She received one dose of IV ceftriaxone, but blood culture was subsequently negative. She was discharged from the clinic with ibuprofen and morphine for break-through pain. The swelling in the right arm resolved at home within 24 h. Discussion: This patient was a young girl with sickle cell disease who presented with fever and limb swelling after a second vaccination with both PPSV23 and the meningococcal conjugate vaccine. Of note, she had received multiple doses of pneumococcal vaccines, and the PPSV23 vaccination associated with this event was administered only 2.5 years after the previous PPSV23-earlier than the 3 years recommended by guidelines. Additionally, she was 5 years old at the time of the limb swelling, much younger than those in previous reports of limb swelling after PPSV23 vaccination. The limb swelling described above can be classified as a local reaction due to vaccination as defined by The Brighton Collaboration Local Reaction Working Group for Swelling at or Near Injection Site. With a score of three from the Naranjo Algorithm for determining adverse events, the case report described above could be considered an adverse drug event. Since the swelling occurred in the same arm as the PNEUMOVAX23 injection and since it was the second PNEUMOVAX23 vaccination, it was likely that PNEUMOVAX23 caused the adverse event. It is possible that administering PNEUMOVAX23 earlier than the recommended 3 years of repeated exposures to polysaccharide capsule antigens might have been contributing factors. Additionally, the immune reaction might have been amplified by the conjugated meningococcal vaccine administered concurrently in the other arm. Finally, the pain that occurred before and during the arm swelling might have been at least partially related to sickle cell vaso-occlusion. Additional information has been requested.