Antisynthetase Syndrome; acute interstitial pneumonitis; Acute progressive shortness of breath with walking a couple of blocks; short of breath while talking; mild cough with mild sputum production; night sweats; acute hypoxemic respiratory failure; severely hypoxic; tachypnea; sinus tachycardia; leukocytosis; Skin exam showed hyperkeratotic skin changes at fingertips consistent with mechanic's hand; diffuse bilateral ground-glass alveolar and interstitial infiltrates; mediastinal adenopathy; unprovoked deep vein thrombosis (DVT).; pulmonary embolism; This case was reported in a literature article and described the occurrence of antisynthetase syndrome in a 68-year-old male patient who received Herpes zoster (Shingrix) for prophylaxis. Co-suspect products included PNEUMOCOCCAL VACCINE POLYSACCHARIDE 23 VALENT (PNEUMOVAX) for prophylaxis.   The patient's past medical history included rheumatoid arthritis (Family History) (in his grandmother and sister), alopecia (Family History) (son), tonsillectomy, hernia repair and ex-smoker (former smoker who quit 35 years ago with ten pack-year).   On an unknown date, the patient received Shingrix and PNEUMOVAX. On an unknown date, 2 days after receiving Shingrix, the patient experienced antisynthetase syndrome (serious criteria hospitalization), acute interstitial pneumonitis (serious criteria hospitalization and GSK medically significant), exertional dyspnea (serious criteria hospitalization), shortness of breath (serious criteria hospitalization), productive cough (serious criteria hospitalization), night sweat (serious criteria hospitalization), acute hypoxic respiratory failure (serious criteria hospitalization and GSK medically significant), hypoxia (serious criteria hospitalization and GSK medically significant), tachypnea (serious criteria hospitalization), sinus tachycardia (serious criteria hospitalization), leukocytosis (serious criteria hospitalization), mechanic's hand (serious criteria hospitalization), bilateral pulmonary infiltrates (serious criteria hospitalization), lymphadenopathy mediastinal (serious criteria hospitalization), deep vein thrombosis (serious criteria hospitalization and GSK medically significant) and pulmonary embolism (serious criteria hospitalization and GSK medically significant). The patient was treated with oxygen (High Flow Oxygen Therapy), methylprednisolone, prednisone, mycophenolate mofetil, enoxaparin, bivalirudin, immunosuppressants nos (Immunosuppressive Therapy (Nos)) and atovaquone. On an unknown date, the outcome of the antisynthetase syndrome, acute interstitial pneumonitis, exertional dyspnea, shortness of breath, productive cough, night sweat, acute hypoxic respiratory failure, hypoxia, tachypnea, sinus tachycardia, mechanic's hand, bilateral pulmonary infiltrates, lymphadenopathy mediastinal, deep vein thrombosis and pulmonary embolism were recovering/resolving and the outcome of the leukocytosis was recovered/resolved.   The reporter considered the antisynthetase syndrome, acute interstitial pneumonitis, exertional dyspnea, shortness of breath, productive cough, night sweat, acute hypoxic respiratory failure, hypoxia, tachypnea, sinus tachycardia, leukocytosis, mechanic's hand, bilateral pulmonary infiltrates, lymphadenopathy mediastinal, deep vein thrombosis and pulmonary embolism to be possibly related to Shingrix.     Additional Information: GSK Receipt Date: 22-Jun-2022 Author's Comment: The patient's family history was remarkable for rheumatoid arthritis in his grandmother and sister; his son had alopecia. The patient denied any significant medical history. The patient surgical history was notable for tonsillectomy and hernial repair. The patient was a former smoker who quit 35 years ago with ten pack-year smoking history.  The patient presented with progressive shortness of breath over 2-3 weeks. The patient's symptoms started two days after receiving pneumococcal (Pneumovax) and zoster (RZV, Shingrix) vaccines. The patient reported feeling quite well until his respiratory symptoms started. Initially, the patient had shortness of breath (SOB) with walking a couple of blocks; by the time he presented to author's institution, the patient was short of breath while talking. The patient reported a mild cough with mild sputum production. The patient also endorsed night sweats, however no fever. The patient denied muscle weakness, muscle pain, joint pain, oral ulcers, skin rash, dysphagia, or Raynaud symptoms. The patient denied recent sick contacts. The patient was evaluated initially at a different medical center where he presented with acute hypoxemic respiratory failure due to unclear etiology. The patient did not respond to initial management and had worsening oxygen requirements. The patient was transferred to author's institution for further workup including evaluation for a lung transplant. Upon presentation to institution, the patient was severely hypoxic and required up to 60 liters 100% FIO2 of high-flow oxygen. The patient's other vitals showed tachypnea with respiratory rate 22-30, temperature max 99.2, sinus tachycardia with heart rate 120, and normal blood pressure. The patient's lungs were clear to auscultation bilaterally, with no rhonchi. Skin exam showed hyperkeratotic skin changes at fingertips consistent with mechanic's hand. The patient's initial comprehensive metabolic panel (CMP) and complete blood count (CBC) were unremarkable except for leukocytosis. The patient tested negative for SARS-CoV-2 COVID-19 twice and bronchoalveolar lavage (BAL) was negative for infections. Chest X-ray (CXR) showed diffuse bilateral ground-glass alveolar and interstitial infiltrates with bibasilar prominence and mediastinal adenopathy. Chest computed tomography (CT) scan showed findings consistent with pneumonitis. Further laboratory results were significant for elevated lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aldolase and positive Anti-Jo-1 antibody. The patient's microbial cell-free DNA molecular testing (Karius) was negative. The patient's presentation raised suspicion for acute interstitial pneumonitis, most likely secondary to inflammatory myopathy. The patient received pulse dose methylprednisolone 1 g intravenous daily for three days, which was subsequently transitioned to prednisone 60 mg daily, in addition to high dose Mycophenolate mofetil. The patient was also started on Atovaquone for Pneumocystis jirovecii (PJP) prophylaxis. The patient was receiving therapeutic doses of enoxaparin for a recent diagnosis of unprovoked deep vein thrombosis (DVT). The patient was switched to bivalirudin as a result of the finding of positive heparin antibodies. The patient's CT chest showed low burden subsegmental pulmonary embolism, for which he underwent inferior vena cava (IVC) filter placement. Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA-19-9) levels were elevated; however extensive evaluation including positron emission tomography (PET) scan and magnetic resonance imaging (MRI) abdomen did not reveal an underlying malignancy. A diagnosis of acute interstitial pneumonitis most likely secondary to anti-synthetase syndrome was made based on positive anti-Jo-1 antibody, elevated aldolase, ALT, LDH, and mechanic's hand features. The patient significantly improved with therapy; his oxygen requirements markedly decreased. The patient was eventually discharged from the hospital on minimal oxygen support. The patient participated in an outpatient pulmonary rehabilitation program during which he showed consistent improvement in physical endurance and was eventually completely weaned off oxygen. The patient remained on maintenance immunosuppressive therapy. The patient's labs remained stable and follow-up chest CT six months later demonstrated near-complete resolution of initial findings. The author described for the first time an alleged temporal relationship between the administration of Pneumovax and Shingrix vaccines and the development of ASS. Due to the relative rarity of autoimmune conditions compared to vaccine administrations, and due to the wide variability of patients' ages, along with the varying durations of the reported latency periods, it was very hard to draw conclusions about whether vaccines play a role in the development of autoimmune conditions. Additional supportive information: This article corresponding to this case is not available for regulatory submission due to copyright restriction.