Sex: F
Vaccine: FLUX
Symptoms: Acute motor axonal neuropathy, Anti-SRP antibody positive, Antibody test positive, Antinuclear antibody negative, Areflexia
Clinical narrative: Initial unsolicited report received from a literature article on 31-Aug-2018 and additional information was received on 03-Sep-2018. Abstract: Immune-mediated necrotizing myopathy is a very rare inflammatory disease affecting skeletal muscles. Immune-mediated necrotizing myopathy may be associated with myositis-specific autoantibodies including anti-single recognition particle and anti-3-hydroxy-3- methylglutaryl-coenzyme A reductase, infectious agents (HIV or hepatitis C), other connective tissue disorders (such as scleroderma), and malignancy. We reported a 28-year old healthy woman presented with subacute onset ascending muscle weakness 2 weeks after an annual influenza vaccination. Cerebral Spinal Fluid study showed normal cell counts with elevated protein and nerve conduction study showed reduced diffuse compound muscle action potential amplitudes suggesting a diagnosis of Guillain-Barré syndrome. Despite treatment using intravenous immunoglobulin, her condition continued to get worse with new bulbar and respiratory muscle weakness. Eventually, the diagnosis of anti-single recognition particle-mediated necrotizing myopathy was made based on elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing. Our patient responded to the combination of intravenous immunoglobulin, prednisone, and anti-CD20 monoclonal antibody, rituximab. Discussion: The IIMs comprise a group of autoimmune disorders, which include polymyositis, dermatomyositis, inclusion body myositis, nonspecific myositis, and IMNM. Women are 2 times more likely to be affected. 1, 9 IMNMs may be associated with several different entities including malignancy, viral infection such as hepatitis C and HIV, and connective tissue disorders such as scleroderma. Some patients with IMNM are found to have myositis-specific antibodies including autoantibodies against SRP, 2, 3 as seen in this patient, and against HMGCR especially in statin-exposed patients. GBS has a known association with influenza vaccination, 10 often presenting with subacute onset ascending paralysis with bulbar involvement and normal cell counts with elevated CSF protein. Therefore, she was treated as a case of post vaccination GBS initially. However, lack of response to IVIg, continued progressive worsening beyond 4 weeks rather than monophasic course, and persistent elevated CK suggested another vaccination-associated disease that is independent of AMAN. Conclusion: We here reported a case of a 28-year-old previously healthy woman who presented with features of AMAN 2 weeks after receiving an annual influenza vaccination, which worsened despite IVIg therapy. Her diagnosis of IMNM was supported by elevated CK, necrotic myofibers with minimal inflammation on muscle disease, and positive anti-SRP serology. IVIg and rituximab may be a useful treatment modality for anti-SRP myositis, a well-known form of myopathy that is resistant to steroid and other standard of care modalities. This case involves a 28 years old female patient who experienced anti-single recognition particle-mediated necrotizing myopathy and acute motor axonal neuropathy, while she received vaccine Influenza Vaccine. The patient's past medical history, medical treatment(s), vaccination(s) and family history were not provided. The patient had no family history of neuromuscular disorders. The patient had no exposure to cholesterol-lowering agents, including statins, herbal medication, or recreational drugs. On an unknown date, the patient received a dose of suspect Influenza Vaccine produced by unknown manufacturer lot number not reported. On an unknown date ¸the patient developed a serious anti-single recognition particle-mediated necrotizing myopathy (immune-mediated necrotizing myopathy), two-weeks following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious acute motor axonal neuropathy following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious new bulbar and respiratory muscle weakness/her muscle weakness began in the calves and thighs and spread rostrally to her trunk and arms (respiratory muscle weakness), 3 weeks following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious her condition continued to get worse with new bulbar and respiratory muscle weakness (condition aggravated), one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date ¸the patient developed a serious elevated creatine kinase (blood creatine phosphokinase increased), two-weeks following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, 5 weeks post vaccination the patient developed a serious she could not lift her arms or legs (mobility decreased). The patient was hospitalized for this event. On an unknown date¸ the patient developed a serious mild muscle tenderness (myalgia) one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious significant head drop (dropped head syndrome) one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date ¸the patient developed a serious dyspnea (dyspnea) one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious dysphagia one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious 20-pound weight loss (weight decreased) one month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious fatigue one-month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious diffuse muscle atrophy following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious respiratory failure atrophy following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious hypophonia (dysphonia) one month following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date¸ the patient developed a serious proximal weakness in her upper and lower extremities (muscular weakness), 2 weeks following the administration of Influenza Vaccine. The patient was hospitalized for this event. On an unknown date, the patient developed a serious muscle edema (muscle oedema) 2 weeks following the administration of Influenza Vaccine. The patient was hospitalized for this event. Relevant laboratory test results included: Blood creatinine - On an unknown date: 16095 U/L [normal less than 198]; on an unknown date: 11699 U/L; on an unknown date: 960 U/L. Protein total - On an unknown date: 99 mg/dL [cerebral spinal fluid revealed elevated total protein]. Troponin - On an unknown date: 3.6 ng/mL. (Other relevant tests included Cerebral Spinal Fluid study showed normal cell counts with elevated protein on an unknown date. Nerve conduction study showed reduced diffuse showed compound muscle action potential amplitudes suggesting a diagnosis of Guillain-Barre syndrome. Elevated creatine kinase, thigh magnetic resonance imaging, muscle biopsy, and positive antibody testing made the diagnosis of anti-single recognition particle-mediated necrotizing myopathy. On an unknown date, physical examination showed her vital signs were stable. On an unknown date, Neurological examination showed marked proximal weakness in her upper and lower extremities: strength of 4/5 in the Medical Research Council (MRC) scale in neck flexion, mild bifacial weakness, 3/5 in proximal upper and lower extremities but 5/5 in her hands and feet. Reflexes were absent in the upper extremities and 1plus in the lower extremities. Electromyography showed abundant fibrillation potentials and positive sharp waves in all tested muscles, and diffuse myopathic units. Echocardiogram and cardiac magnetic resonance imaging (MRI) were unremarkable without signs of myocarditis or pericardial effusion. Thigh MRI showed diffuse edema on Short T1 Inversion Recovery and T2 sequences. Extensive rheumatologic workup showed normal complements C3, C4, and all but one of the myositis-specific antibodies (Jo-1, PL-7, PL-12, Mi-2, Ku, EJ, and OJ) returned negative, including SS-A, SS-B, DNA, RNP, Smith, ANA, and anti-HMGCR. Motor examination showed significant improvement with mild proximal weakness 4-4+/5 in MRC score in the deltoid, biceps, iliopsoas, and hamstring muscles. Motor exam this time showed (in MRC): deltoid 1/5, biceps 3/5, triceps 2/5, wrist flexion 42/5, wrist extension 4-5, abductor pollicis brevis 4/5, first dorsal interosseous 4/5, iliopsoas 1/5, quadriceps 3/5, hamstring 3/5, ankle dorsiflexion, and plantar flexion 4/5 bilaterally Chest and abdominal Computed Tomography scans, performed to exclude occult malignancy, found a retroperitoneal mass.). Lymphocytic inflammatory cell infiltration was absent. There was no evidence of perifascicular atrophy or increased endomysial fibrosis. The mass was surgically resected and confirmed to be a benign schwannoma. Final diagnosis was acute motor axonal neuropathy and anti-single recognition particle-mediated necrotizing myopathy. The patient was treated with Prednisone at a dose of 40 mg and Rituximab at a dose of 375 mg/m2 weekly. The patient was treated with a five-day course of intravenous immunoglobulin (IVIg) dose of 2 g/kg with minimal improvement. The patient was discharged to a long-term rehabilitation facility and required feeding tube insertion. The patient was also given a combination of IVIg and Rituximab  she slowly demonstrated clinical improvement and down trending of serial CK levels, from 11,700 to 960 U/L after 5 weeks. Monthly IVIg was continued along with Rituximab every 6 months and her steroid was gradually tapered off while in a rehabilitation facility and series of corticosteroids. Ophthalmic, cardiac, pulmonary, and abdominal examinations were unremarkable except for mild sinus tachycardia on Electrocardiogram. Shortly after admission, she was started on intravenous SOLU-MEDROL (1 g daily for 5 days). The patient outcome is reported as recovering for all the events.; Sender's Comments: This case involves a 28 years old patient who received Influenza vaccine (unknown manufacturer) and presented with Immune-mediated necrotising myopathy, acute motor axonal neuropathy, respiratory muscle weakness, condition worsened, Creatine kinase increased, mobility decreased, myalgia, dropped head syndrome, dyspnoea, dysphagia, Weight decreased, fatigue, dysphonia, muscular weakness, muscle oedema after vaccination. Time to onset is unknown. More details regarding patient's medical history, condition at the time of vaccination, lab test and etiological workup to identify alternative etiology are needed for complete assessment of the case. Based on the available information the role of vaccine cannot be assessed.