Age: 33.0
Sex: F
Vaccine: FLUX(H1N1), FLUX(H1N1)
Symptoms: Anti-cyclic citrullinated peptide antibody positive, Antinuclear antibody negative, Antinuclear antibody positive, Arthralgia, C-reactive protein increased
Clinical narrative: This medically confirmed literature report (initial receipt 24-Jun-2016) concerns a 33 year old female patient. The patient had no significant past medical history. The patient was referred to a rheumatology clinic in May 2010 by her primary care physician for having pain and swelling in multiple joints since November 2009. Patient received a seasonal flu shot in October and a week later, she noted some joint pain and aches in hands, wrists, and knees, which resolved within a few days and patient became asymptomatic. A month later, she received H1N1 (swine influenza) vaccine and a week after started experiencing joint pain, swelling, and stiffness in hand, wrist, elbow, shoulder, and knee joints. She also complained of significant morning stiffness that last for more than one hour. 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. She fulfilled most of the criteria for classification of RA based on the guidelines. Laboratory findings initially included an erythrocyte sedimentation rate (ESR) of 24 mm/hr, rheumatoid factor (RF) of 26 IU/mL, C-reactive protein (CRP) of 1.3mg/dL, cyclic citrullinated peptide (CCP) IgG of 212. Her basic chemistry, liver function tests, hemoglobin, and complement levels were essentially within normal limits. Serological tests were positive for antinuclear antibody (ANA), RF, anticyclic citrullinated peptide (anti-CCP) and negative for SSA, SSB, hepatitis C virus, parvovirus B19 and being immunized for hepatitis B. 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 40mg daily, which partially helped with symptoms in the beginning with eventual relapse of symptoms. Later she 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) were 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 5-10 minutes. However, her pain was controlled only while she was on steroid therapy for 3 weeks and had returned thereafter. Later she was switched to golimumab (TNF-alpha inhibitor) 50mg once monthly subcutaneously. Her methotrexate dose was also increased to 12.5mg weekly. At her third visit her symptoms were much improved and her ESR and CRP were also within normal limits. Reporter's Comments: Reporter comment: A causal relationship has not been confirmed between swine-flu vaccine and onset of RA, but there is a temporal connection between the two. There might also be a synergetic effect of seasonal flu and swine flu vaccines. Genetically, RA has consistently been associated with an epitope in the third hypervariable region of the HLA-DR beta chains, known as the "shared epitope", which is found primarily in DR4 and DR1 regions. The presence of HLA-DRB1 alleles is associated with susceptibility to RA in this group. This patient could be genetically susceptible since she is in this group. Sender's Comments: Company comments: Listedness: Assessment according to the CCDS for CSL Inactivated Influenza Virus Vaccine, Rheumatoid and all related events are unlisted.  Causality: There is a temporal relationship of 1 week following vaccination with seasonal Influenza vaccination. Clinical presentation and laboratory findings were consistent with Rheumatoid Arthritis although the diagnosis was made after 2nd presentation following H1N1 vaccination. Investigations excluded secondary causes.  Although causally not proven, there is biological plausibility by vaccination triggering autoimmune response by molecular mimicry or nonspecific activation of T-mediated cellular response in predisposed individuals. Listedness: Assessment according to the CCDS for CSL's H1N1 Influenza Vaccine, Rheumatoid arthritis and all related events are unlisted. Causality: There is a temporal relationship of 1 week following vaccination with H1N1 vaccination. Clinical presentation and laboratory findings were consistent with Rheumatoid Arthritis although the diagnosis was made after 2nd presentation following H1N1 vaccination. Investigations excluded secondary causes.  Although causally not proven, there is biological plausibility by vaccination triggering autoimmune response by molecular mimicry or nonspecific activation of T-mediated cellular response in predisposed individuals.