Sex: F
Vaccine: FLUX
Symptoms: Myositis, Oedema peripheral, Pain in extremity, Pathology test, Periorbital swelling
Clinical narrative: Antisynthetase Syndrome; Autoimmune syndrome induced by adjuvants" (ASIA syndrome); Autoimmune syndrome induced by adjuvants" (ASIA syndrome); facial and periorbital swelling; periorbital swelling; mild shortness of breath; bilateral hip pain; severe dyspnea both on exertion and at rest; Dyspnoea at exertion; bilateral edema of the hands; diffuse hyperpigmentation of hands/hyperpigmentation of her hands; severe muscle weakness/weakness primarily in proximal musculature; inability to lift hip and shoulder musculature progressing to difficulty using the gas pedal when driving; extensive myofiber necrosis and regeneration; synovitis of the metacarpal phalangeal joints bilaterally; significant tenderness to palpation over the thighs bilaterally; symmetric muscle inflammation/myositis panel was obtained, which was positive for antiJo-1; necrotizing myopathy; Edema face; bilateral crackles on auscultation; interstitial disease pattern on chest x-ray film.; This case was reported in a literature article and described the occurrence of antisynthetase syndrome in a 46-year-old female patient who received Flu Seasonal QIV Dresden (Influenza vaccine Quadrivalent 2017-2018 season) for prophylaxis.   In November 2017, the patient received Influenza vaccine Quadrivalent 2017-2018 season. On an unknown date, less than a week after receiving Influenza vaccine Quadrivalent 2017-2018 season, the patient experienced antisynthetase syndrome (serious criteria hospitalization), autoimmune disorder (serious criteria hospitalization and GSK medically significant), reaction to excipient (serious criteria hospitalization), facial swelling (serious criteria hospitalization), periorbital swelling (serious criteria hospitalization), shortness of breath (serious criteria hospitalization), pain in hip (serious criteria hospitalization), dyspnea at rest (serious criteria hospitalization and GSK medically significant), exertional dyspnea (serious criteria hospitalization), edema hands (serious criteria hospitalization), skin hyperpigmentation (serious criteria hospitalization), muscle weakness (serious criteria hospitalization), mobility decreased (serious criteria hospitalization), muscle necrosis (serious criteria hospitalization and GSK medically significant), synovitis (serious criteria hospitalization), tenderness (serious criteria hospitalization), muscle inflammation (serious criteria hospitalization), myopathy (serious criteria hospitalization), face edema (serious criteria hospitalization), crackles lung (serious criteria hospitalization) and interstitial lung disease (serious criteria hospitalization and GSK medically significant). The patient was treated with prednisone, naproxen and intravenous fluid (nos) (Intravenous Hydration). On an unknown date, the outcome of the antisynthetase syndrome, autoimmune disorder, reaction to excipient, facial swelling, periorbital swelling, shortness of breath, pain in hip, dyspnea at rest, exertional dyspnea, edema hands, skin hyperpigmentation, muscle weakness, mobility decreased, muscle necrosis, synovitis, tenderness, muscle inflammation, myopathy, face edema, crackles lung and interstitial lung disease were recovered/resolved.   The reporter considered the antisynthetase syndrome, autoimmune disorder, reaction to excipient, facial swelling, periorbital swelling, shortness of breath, pain in hip, dyspnea at rest, exertional dyspnea, edema hands, skin hyperpigmentation, muscle weakness, mobility decreased, muscle necrosis, synovitis, tenderness, muscle inflammation, myopathy, face edema, crackles lung and interstitial lung disease to be related to Influenza vaccine Quadrivalent 2017-2018 season.  Additional details were reported as follows: This case was reported in a literature article and described Antisynthetase Syndrome in a 46 years old female patient, who was vaccinated with unspecified Influenza vaccine (Manufacturer unknown) for prophylaxis.  The patient had no significant medical history. No information on patient's family history or concomitant medication or concurrent condition was provided. On an unspecified date in November 2017, the patient received routine dose of unspecified Influenza vaccine (Route and site of administration unspecified; batch number not provided). The age at vaccination was not provided. On an unspecified date, within the next 2 days of vaccination, the patient experienced facial and periorbital swelling, which was associated with mild shortness of breath and bilateral hip pain. The patient was prescribed naproxen with mild improvement in hip pain. In the following 3 weeks, the patient's symptoms progressed with worsening facial swelling and severe dyspnea both on exertion and at rest. The patient also reported bilateral edema of the hands and diffuse hyperpigmentation. The patient also complained of severe muscle weakness with inability to lift hip and shoulder musculature progressing to difficulty using the gas pedal when driving. These symptoms prompted her visit to the emergency department. On initial triage, the patient was noted to be normotensive, afebrile, and saturating well on room air. On physical examination, the patient was found to have periorbital swelling and edema of her face. Respiratory examination was notable for bilateral crackles on auscultation. Musculoskeletal and integumentary examination revealed hyperpigmentation of her hands with mild synovitis of the metacarpal phalangeal joints bilaterally. The patient was noted to have significant tenderness to palpation over the thighs bilaterally with associated weakness primarily in proximal musculature. Laboratory values revealed as total creatine kinase level of 24,285 U/L with aspartate aminotransferase of 19 U/L and alanine aminotransferase of 537 U/L. On imaging, the patient was found to have an interstitial disease pattern on chest x-ray film. At this time, the patient was started on oral prednisone 60 mg daily and aggressive intravenous hydration. A myositis panel was obtained, which was positive for anti-Jo-1, determined by line blot testing with a reference value of positive greater than 1, with a titer of more than 8.0 and a negative antinuclear antibody result as detected by indirect immunofluorescence test on HEp-2 cells. During the patient's hospital stay, the patient's respiratory symptoms markedly improved; however, the weakness and pain of her thighs persisted. A magnetic resonance imaging scan of the thighs was obtained, which revealed symmetric muscle inflammation. At this point, an anterior thigh biopsy was performed. The thigh tissue was remarkable for extensive myofiber necrosis and regeneration. The pathology appeared to be primarily necrotizing myopathy with limited inflammation. This prompted human leukocyte antigen class I immunohistochemistry staining, which was positive and consistent with an immune-mediated myopathic disorder. The patient's symptoms improved, and the patient was discharged on prednisone 60 mg daily with the plan to follow up in the outpatient rheumatology office. The patient was referred for pulmonary function testing, which was normal. Within 4 weeks, the patient's muscle pain and weakness slowly improved. Within 8 weeks, the patient's inflammatory markers, including creatinine kinase and aldolase, normalized. Over the course of the next 6 months, the patient was prescribed a slow steroid taper from 60 mg, and the symptoms did not recur. The patient did not require any additional immunosuppressive agents. The patient was advised to avoid the influenza vaccination in the future. This case has been considered as serious due to hospitalization. The authors commented, "A previously healthy 46-year-old woman without any risk factors or family predisposition to autoimmune diseases developed antisynthetase syndrome. After extensive investigation, the only inciting factor that could explain her symptoms was the administration of the influenza vaccination 1 week prior to her onset of symptoms. The acuity from the administration of the vaccine, clinical picture of myositis, and positive biopsy findings with appearance of autoantibodies fulfills both major and minor criteria in the diagnosis of ASIA syndrome. ASIA has been implicated in the development multiple distinct autoimmune processes. Vaccines, including hepatitis B vaccine, bacillus Calmette-Guerin, tetanus, influenza, smallpox, poliomyelitis, and diphtheria, have been associated with polymyositis and dermatomyositis. Specific adjuvants that have been implicated are silicone, tetramethylpentadecane, pristane, and aluminum. The interstitial pattern on chest x-ray film, clinical picture of myositis with hyperpigmentation, myofiber necrosis on biopsy, and the high-titer anti-Jo-1 antibodies suggest antisynthetase syndrome, which has not been implicated in ASIA prior. Patients who met these criteria were included in an ASIA registry, which was formed with the intention to compare cases to obtain a better understanding of this phenomenon. Information from this registry showed that the duration from exposure to offending agent to onset of symptoms varied between 3 days and 5 years, with the average onset occurring in 16.8 months. The case of vaccines the latency should be days, whereas other environmental triggers should be within a month. The clinical significance of myositis induced by influenza vaccine is unclear at the moment. For the case described, the patient's symptoms improved with steroid monotherapy. Generally, the mainstay of treatment for antisynthetase syndrome is glucocorticoids; however, additional immunosuppressants such as methotrexate and azathioprine are often needed for disease control. Use of other immunosuppressants such as rituximab has been seen in certain cases to be effective in improving the pulmonary status in patients with advanced interstitial lung disease. In the case described above, the patient's symptoms improved within several weeks without the need for additional disease-modifying agents. Initially, her pulmonary complaints improved within days without the need for supplemental oxygen therapy. While the muscular symptoms required a long taper of glucocorticoid therapy, ultimately her symptoms eventually resolved. We hope that the case described, although a single case without any control, would lead to further research in not only the etiology and recognition of ASIA, but also further research in regard to treatment options. Specifically, it would be interesting to determine if a more conservative approach to immunosuppression without the use of biologics or disease-modifying antirheumatic drugs would lead to adequate remission in patients with IIM due to adjuvants".