Sex: F
Vaccine: FLUX(H1N1), FLUX(H1N1)
Symptoms: Liver function test normal, Musculoskeletal stiffness, Parvovirus B19 test negative, Red blood cell sedimentation rate increased, Rheumatoid arthritis
Clinical narrative: Case number PHHY2016US116722, is a literature report initially received as spontaneous report from the Vaccine Adverse Event Reporting System (VAERS reference number: 640801) website on 23 Aug 2016. The author discussed about the first reported case of a female who developed rheumatoid arthritis (RA) right after vaccination with H1N1 swine influenza vaccine. This report refers to a 33 years old female patient with no significant past medical history. Prior vaccination history included administration of seasonal influenza vaccine (manufacturer and batch number: unknown) in Oct 2009 following which she had joint pain, aches in hands, wrists and knees (see related case number: PHHY2016US118163). Her concomitant medications were not reported. The patient was vaccinated with H1N1 swine influenza vaccine (manufacturer and batch number: not reported) in Nov 2009. The patient experienced joint pain, swelling and stiffness in hand, wrist, elbow, shoulder and knee joints, a week after vaccination. She complained of significant morning stiffness that lasted more than one hour. Since Nov 2009, she was having pain and swelling in multiple joints and she was referred to the rheumatology clinic in May 2010 by her primary care physician (PCP). On physical examination she had bilateral synovitis in fourth and fifth metacarpophalangeal (MCP), second and third proximal interphalangeal (PIP) joints, with prominent left ulnar styloid. The patient fulfilled most of the criteria for classification of rheumatic arthritis (RA) based on guidelines. Laboratory findings included an erythrocyte sedimentation rate (ESR) of 24 mm/hr (normal range unspecified), rheumatoid factor (RF) of 26 IU/mL (normal range unspecified), C reactive protein (CRP) of 1.3 mg/dL (normal range unspecified, cyclic citrullinated peptide (CCP) Immunoglobulin G (IgG) of 212 (units and normal range unspecified). Her basic chemistry, liver function tests, hemoglobin and complement levels were essentially within normal limits. The serological tests were positive for antinuclear antibody (ANA), rheumatoid factor and anticyclic citrullinated peptide (anti CCP) (results unspecified) and negative for SSA, SSB, hepatitis C virus, parvovirus B19 and being immunized for hepatitis B (other manufacturer, batch number: not reported). Her radiological findings were negative for any joint effusion or destruction. On initial presentation to her PCP, she was given a 10-day course of prednisone 40 mg daily which partially helped with symptoms in the beginning with eventual relapse of symptoms. Later patient was started on methotrexate 7.5 mg weekly along with a short duration (3 weeks) of low dose prednisone with daily folic acid and calcium/vitamin D supplementation. During her follow up visit about 2 months later, her disease activity score (DAS) was 4.83 and number of tender joints was 7 and number of swollen joints were 5, with significant improvement in morning stiffness which lasted for 5 to 10 minutes. However, her pain was controlled only while she was on steroid therapy for 3 weeks and had returned thereafter. Later the patient was switched to golimumab (TNF alpha inhibitor) 50 mg once monthly subcutaneously. Her methotrexate dose was also increased to 12.5 mg weekly. At her third visit, her symptoms were much improved and her ESR and CRP were also within normal limits. The seriousness of the events was not reported, but the event RA was upgraded as medically significant based on the information available in the NVS-IME list. The author stated that there might be a synergetic effect of seasonal flu and swine flu vaccines in this study. Genetically, RA was consistently been associated with an epitope in the third hypervariable region of the human leukocyte antigen-DR beta chain (HLA-DR beta chains), known as the shared epitope, which was found primarily in DR4 and DR 1 regions. The presence of HLA-DRB1 alleles was associated with susceptibility to RA in certain groups. Hence certain individuals with the presence of the "shared epitope" might develop RA following specific vaccinations. This patient could possibly be genetically susceptible since she was in this group. The author concluded the article stating that a causal relationship had not been confirmed between swine-flu vaccine and onset of RA, but there was a temporal relationship between the two based on this case report. Follow up information received from author on 19 Sep 2016: Report type changed from spontaneous report to literature report, literature information, events deleted (pain in extremity, pain and inappropriate schedule of vaccine administered) and clinical information.