Sex: M
Vaccine: FLU4
Symptoms: Immunoglobulin therapy, Impaired work ability, Incision site pain, Intervertebral disc protrusion, Liver function test abnormal
Clinical narrative: Based on information received on 05-Jul-2017, the report previously considered as non-valid became valid: patient identifier was reported. Initial unsolicited report received from a healthcare professional on 23-Jun-2017. This case was considered as invalid case as patient identifiers were not reported. This case involves vaccination with a dose of INFLUENZA VACCINE (Batch number, expiration date, dose, dose in series, route and site of administration were not reported) on an unknown date. Medical history and concomitant medication was not reported. On an unknown date, after the vaccination, an auto-immune disorder occurred. Lab data and corrective treatment not reported. Outcome of the event was not reported. Upon internal review the case was considered as serious because of important medical event: an auto-immune disorder. Follow-up report received from a healthcare professional on 05-Jul-2017. 37-year-old male patient was vaccinated with FLU VACCINE (batch number: UI669AA) on 03-Oct-2016 (also reported as 04-Oct-2016). Patient was previously vaccinated with TDAP on 01-Oct-2010 dose one of one. Patient had a medical history of obesity, mononeuritis multiplex and hypertriglyceridemia. On an unknown date, after the vaccination, patient had atypical, chronic, multifocal neuropathy associated with widespread, waxing and waning numbness and paresthesias. On 06-Oct-2016, three days after the vaccination, patient developed a sore throat, numbness and tingling on the right side of his tongue, and motor dysfunction of the left side at this tongue. He was treated with NSAIDs and CLARITIN for a flu shot reaction. Patient's symptoms then improved. Around on 25-Oct-2016, 22 days after the vaccination, patient was asymptomatic. However, in the next week, patient redeveloped numbness in lips and tongue, burning in tongue, intermittent paresthesias in patient's right upper limb, myalgias in patient's left to right upper limbs, and more persistent numbness and tingling in patient's left to right hands and left forearm. On 09-Nov-2016, 37 days patient became aware of new-onset weakness in patient's left upper limb, impairing patient's ability to intubate with patient's left hand and don patient's jacket with patient's left arm. Shortly thereafter, patient developed numbness and continuous, dull, aching pain throughout his left upper limb. Neurological examination on 10-Nov-2016, 38 days after the vaccination, revealed diffuse weakness in his left upper limb. Laboratory studies revealed CK (Creatine Kinase): 395, slightly positive dsDNA antibodies, negative FANA, and normal/negative Lyme antibodies, CRP, ESR, B12 level, and ENA antibodies. MRI of the brain and cervical spine on 16-Nov-2016 were normal except for a disc bulge at C6-7. On middle Nov-2016, after the vaccination, patient developed more persistent numbness and tingling in his right hand, with maximal involvement of right index finger, and left facial weakness. Neurologic examination on 25-Nov-2016, 53 days after the vaccination, patient revealed mild left facial weakness, impaired sensation in the proximal left upper limb, absent left biceps and brachioradialis reflexes, moderate proximal left upper limb weakness, and mild weakness of the left fingers. MRI of the chest on 30-Nov-2016 was unremarkable. On 04-Dec-2016, 62 days after the vaccination, patient developed dysarthria, dysphagia, increased numbness of the tongue and teeth, weakness of the left side of his tongue manifesting with leftward deviation on protrusion, and new numbness and tingling on his left anterolateral torso from his nipple to his hip. He was admitted on 04-Dec-2016. Examination revealed globally reduced or absent stretch reflexes. An electro-diagnostic study of his upper limbs and left lower limb revealed largely normal findings in the left lower limb (no sensory studies performed) and findings in the upper limbs compatible with an active, recent-onset left to right brachial plexopathy. There were no demyelinating findings, except for marked amplitude drops with Erb's point stimulation of the left ulnar and right median nerves. LP (Lipoprotein) was normal except for protein 77 (normal oligoclonal bands, lgO index. IgG synthesis, and ACE). On an unknown date, after the vaccination, patient diagnosed of CIDP (chronic inflammatory demyelinating polyneuropathy) and treated with IVIG 30 gram/day for five days (intravenous immunoglobulin) and intravenous SOLU-MEDROL 250 mg on 05-Dec-2016 and 07-Dec-2017. Patient had a surprisingly rapid response. His speech, swallowing, lingual weakness, and left upper limb weakness all improved prior to discharge. On discharge on 08-Dec-2016, his left tongue was no longer deviating to the left. His left facial weakness had resolved by 06-Jan-2017. As an outpatient, he was continued on IVIG 30 g weekly on 19-Dec-2016, 26-Dec-2016, 02-Jan-2017 and 09-Jan-2017. He was also treated with SOLU-MEDROL 250 mg twice per week for 2 weeks in late Dec-2016. Since that time, his left upper limb weakness, sensory symptoms, and pains have largely resolved, but he has continued to experience intermittent, multifocal numbness and tingling throughout his body, lasting for several hours or days at a time. In early Jan-2017, few months after the vaccination, patient complained of increased numbness and weakness throughout his right upper limb. At a return visit in the neurology clinic on 06-Jan-2017, 95 days after the vaccination, patient was found to have new right elbow extensor weakness. For the last 2-3 weeks, he has had persistent soreness in his hips and calves. On an unknown date, after the vaccination (In the last month), patient had developed progressive numbness and tingling throughout his right foot, sparing his heel, accompanied by milder numbness and tingling throughout his right lower leg to the knee with additional involvement of the right anterolateral thigh. On an unknown date, after the vaccination (In the last few days), patient has had tingling on the ball of his left foot. He had no other sensory symptoms in his left lower limb. On an unknown date, after the vaccination (in the last four weeks), he had developed severe numbness throughout his right medial forearm. On an unknown date, after the vaccination (in the last two weeks), he had developed increased numbness and tingling in his right lateral two fingers, an abnormal "waxy" sensation in his right medial three fingers, and tingling in his right palm. He did not had numbness or tingling in more proximal aspects of his upper limbs. Since at least Jan-2017, few months after the vaccination, patient has had numbness and tingling throughout his right face and right to left lower teeth. Since Dec-2016, after the vaccination, patient had persistent numbness in his left upper lip extending to his left cheek and a patch of numbness on his left lateral trunk, extending from his left hip/waist to his lower rib cage. In the last one and half months, this numbness had increased in intensity and spread. He was continuously sore in this region. His left abdominal wall was "bulging." Over the past 3 to 4 months, patient has had more intermittent numbness and tingling in his right lower truncal and abdominal region. Right triceps weakness was improving. Since Feb-17, few hours after the vaccination, he had developed progressive weakness in his legs, with primary involvement of his right hip flexors. On an unknown date, after the vaccination, patient had fallen on several occasions. Patient can no longer perform a sit up. IVIG was restarted at 30 g weekly on 31-Jan-2017, 07-Feb-2017, and 14-Feb-17. On 22-Feb-2017 to 25-Feb-2017, he was treated with IVIG 50 g daily for 4 days. He was then after being treated with IVIG 2 g/kg every month. He received additional Mg infusions over the past three days. A repeat electro-diagnostic study of his upper limbs on 23-Jan-2017 revealed normal findings except for low-amplitude sensory responses, worse on the left than the right. There were no demyelinating findings, apart from a possible right median partial motor conduction block in the forearm. Additional laboratory studies in Feb-2017 revealed normal or negative HJV antibodies, CBC, ESR, and serum protein IFE. CK was 416. CMP (Comprehensive Metabolic Panel) was normal except for AST (Aspartate Aminotransferase) 53. On an unknown date in Mar-2017, few months after the vaccination, neurological examination showed that patient developed global areflexia except for intact right ankle jerk, mildly to moderately weak finger extensor muscles (worse on the right), moderately weak hip flexor muscles (worse on the right), mild toe extensor weakness (worse on the right), impaired right heel walking, and patchy sensory loss throughout the body. An electro-diagnostic study revealed findings consistent with an active and chronic, diffuse, axonal, sensory-motor, non-length-dependent (asymmetric and multifocal), polyradiculoneuropathy involving the cervical, thoracic, and lumbosacral regions. In the lower thoracic region, denervation predominated on the left. In the distal lower limbs, there was accentuated involvement in the right common peroneal nerve distribution. As per the physician, from Nov-2016, after the vaccination, patient was suffering from atypical, chronic, relapsing and remitting, multifocal, predominantly axonal, sensory-motor polyradiculoneuropathy affecting the cranial, cervicobrachial, thoracic, and lumbosacral regions, patient had had multiple cranial neuropathies and brachial plexopathies, but these foci of involvement had significantly improved in recent months. In the last 1-2 months, he had been experiencing new, progressive, albeit fluctuating sensory symptoms and weakness in his lower limbs, worse on the right than the left, consistent with a patchy, asymmetric, non-length dependent. Lumbosacral polyradiculoneuropathy. Hence, patient's disease was still active. Patient's neuropathy had commenced shortly after his influenza vaccination in Oct-2016, suggesting but not proving that this vaccination had triggered an autoimmune neuropathy. In the absence of EMG/nerve conduction findings consistent with a primary demyelinating neuropathy, it could not diagnose Lewis Sumner syndrome (multifocal CIDP). From an etiologic perspective, patient's phenotype was most concerning for PNS vasculitis or neurosarcoidosis.The primary arguments against neurolymphomatosis were patient's multiple spontaneous or IVIG-induced remissions of individual nerve involvement. Non-cellular CSF (cerebrospinal fluid) in Dec-2016, and negative MRIs in Dec-2016. To further evaluate Patient's condition, physician recommended additional blood work, updated CSF analyses, updated MRIs of the brain and spine, and a nerve or nerve/muscle biopsy. Although a right medial antebrachial cutaneous nerve biopsy was considered and till then monthly IVIG infusions at an unchanged dose. Patient completed his monthly cycle of IVIG on 29-Mar-2017 and 30-Mar-17. Patient has had no further IVIG. The right superficial peroneal nerve and peroneus brevis muscle biopsies were performed on 26-Apr-2017. In addition to a number of postsurgical and/or preparatory artifactual changes, the nerve biopsy demonstrated alterations indicative of an active axonal neuropathy, including a mild, uniform loss of myelinated nerve fibers; unequivocally increased active axonal degeneration in the semithin and teased nerve fiber preparations; frequent older myelin ovoids in the semithin sections; and sparse axonal atrophy. Considering the paucity of regenerating axonal clusters in the semithin sections and regenerating fibers in the teased nerve fiber examination, the neuropathy was likely recent in onset and/or proximal in localization. The connective tissue elements were unremarkable, apart from diffuse, nonspecific subperineurial edema in all fascicles; a few foci of mild-to-moderate perineurial thickening, sometimes accompanied by small collections of mononuclear inflammatory cells, consistent with a mild, multifocal perineuritis; and a few, generally small, mononuclear, perivascular inflammatory aggregates in the epineurium . In combination, the findings of a highly active axonal neuropathy, mild focal perineuritis and perineurial damage, and mild epineurial perivascular inflammation raised concern for but were not diagnostic of a vasculitic neuropathy. There was no definite vasculitis or granulomatous inflammation. The muscle biopsy revealed alterations indicative of a chronic neurogenic process characterized by denervation atrophy and reinnervation, including many, primarily angulated atrophic fibers of both histochemical fiber types; a few foci of small group atrophy; frequent esterase-positive denervated fibers; occasional target fibers; and fiber type grouping. The only other finding was mild, nonspecific mononuclear, perivascular inflammation adjacent to a few endomysia and perimysial vessels. On an unknown date, after the vaccination, patient was symptomatic from his multifocal neuropathy over the past 1.5 months. Although some symptoms had improved, others had worsened. Addressing his symptoms limb-by-limb, in his right upper limb, patient had developed increased numbness and tingling in his medial three fingers and palm, to the extent that these fingers were then number than his right lateral two fingers. Patient was maximally numb in his right small finger. The numbness in his right anteromedial forearm had remained stable. He had not developed any other new sensory symptoms in his right upper limb, but he had been having right hand cramps. He was still functionally strong in his right upper limb. In his left hand, he still had numbness and tingling in all five fingers and his palm, without significant change. All five fingers were equally affected. He was no longer aware of numbness or tingling in his left forearm or upper arm. He had no subjective weakness in his left upper limb. In his right lower limb, even prior to undergoing the right superficial peroneal nerve biopsy, he had developed progressive numbness throughout his entire right lateral lower leg extending to the knee. The pre-existing, constant, diffuse numbness and tingling in his right foot had not significantly changed. This numbness was maximal in his toes, distal dorsal foot, and ball of his right foot. Since undergoing the right superficial peroneal nerve biopsy, he had not developed any new pains or sensory symptoms in his right foot, apart from occasional "twinges" of cramp-like pain on his right dorsal foot. He was also mildly tender at the site of his biopsy. It was not infected .In his left foot, he had been experiencing "a little," intermittent numbness and tingling in his lateral four toes, but heel symptoms had resolved. He had no sensory symptoms or weakness in other regions of his left lower limb. Patient initially stated that the weakness in his proximal right lower limb had not significantly changed in the last 1.5 months, but on directed questioning, he admitted that he was now entering his SUV more easily with this leg. He no longer had to manually lift the leg. He was still using his arms to push himself up from chairs. He was still mildly compromised in his ability to climb stairs. He takes one step at a time and holds onto the railing. There had been no interval falls, but he had occasional "imbalance episodes." He still had mild difficulty putting in a sock and shoe on his right foot. To do so, he placed the leg on the bed. He had not developed proximal left lower limb weakness. On early Apr-2017, few months after the vaccination, patient had been "flapping" his right foot with ambulation. He continued on light duty at work. Since undergoing the biopsy, he had a work restriction of lifting no more than 10 pounds. He either worked at a desk or helps in the emergency room. He was not allowed to go on ambulance rides. He still had some truncal/core weakness. He still had difficulty transitioning from a lying to sitting position in bed. He cannot perform a sit up. The patch of numbness in his left abdomen, flank, and lower thoracic back region had remained stable, except for "a little" improvement in the flank. In the last week, he had developed persistent numbness in his right abdomen, flank, and back, extending from his lower rib cage to his hip. He did not had numbness or tingling on his chest. He still had numbness and tingling throughout his right face, which had improved. He was no longer experiencing sensory symptoms in his right scalp, which would seem to constitute an interval improvement, but instead, he today stated that he has constant tingling in his left forehead and scalp, which is improving, with the caveat that he did not complain of left scalp numbness on 29-Mar-2017. He did not had numbness/tingling in his left face, except for persistent but improving numbness in his left upper lip. Both of his bilateral upper lips were now equally, mildly numb. He still had a burning sensation on his tongue at all times. Intermittently, he appreciates tingling sensations and "fasciculations" on his lateral tongue bilaterally. He continues to infrequently choke or cough when drinking water or other thin liquids, without change. Bowel and bladder control was intact. He had not developed visual loss, diplopia, hearing loss, vertigo, syncope, presyncope, headaches, cognitive impairment, or other involuntary movements. He had not developed a rash, joint pain/swelling, or any non-neurological symptom. Taste was intact. He did receive IVIG 50 g on 25-Apr-2017; IVIG was then held because of abnormal LFT's. For pain, he had been taking TYLENOL 500 mg thrice a day and Naproxen 500 mg as needed. He has cut back on TYLENOL and naproxen over the past week. Patient required ER/Doctor visit. Other laboratory studies obtained on 29-Mar-2017 revealed normal or negative ANCAs, hepatitis C antibodies, hepatitis B surface antigen, double-stranded DNA antibodies, ACE (angiotensin-converting enzyme) level, rheumatoid factor, CRP (C-reactive protein), MPO (Myeloperoxidase) antibodies, PR3 antibodies, and cryoglobulins. CCP (cyclic citrullinated peptide) antibodies were slightly positive at 21. ANA (Antinuclear Antibody Panel) was slightly positive at 1.9 corresponding to SSA antibodies in the ENA (Extractable Nuclear Antigen Antibodies) screen MRI of the brain, cervical spine, thoracic spine, and lumbar spine on 12-Apr-2017, with and without contrast, was normal except for a small herniated disc at Tl-2 and mild to moderate facet arthropathy at L4-5 and L5-Sl. Lumbar puncture on 14-Apr-2017 revealed 9 nucleated cells (94% lymphocytes}, I RBC, glucose 59, protein  136, ACE 2.2, negative cytology, negative bacterial culture, and negative meningitis/encephalitis  PCR panel, to include HSV, VZV, HHV6, and CMV. Flow cytometry was also performed, but the results are not available.  Blood work on 21-Apr-2017 revealed normal CBC and CMP except for AST 72 and ALC 114. IVIG was then held. CMP on 28-Apr-2017 was normal except for AST 65 and ALT 94. Outcome of event fall was not reported. Patient was recovering from the event sore throat and did not recovered from other events. Sender's Comments: Follow up received on 05-JUL-2017 changes assessment as follows: The patient experienced an autoimmune disorder following a flu vaccination. Time to onset was compatible. Patient's medical history and lab workup along with examination details was reported. As per the available information it could not be established that the condition was due to the vaccine. Further information regarding investigations ruling out possible etiologies is required. Based on the available information the role of the vaccine cannot be assessed.